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1.
Res Sq ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38978574

ABSTRACT

We examined the sex-specific association between education and income with biological age (BA) and by race/ethnicity. The Klemera-Doubal method was used to calculate BA among 6,213 females and 5,938 males aged 30-75 years who were Hispanic, non-Hispanic (NH) White, NH Black (NHB), or NH Asian (NHA). Compared with a college education, less than a high school education was associated with greater BA by 3.06 years (95% CI: 1.58, 4.54) among females only; associations were strongest among NHB, Hispanic, and NHA females. Compared with an annual income of ≥$75,000, an income <$25,000 was associated with greater BA by 4.95 years (95% CI: 3.42, 6.48) among males and 2.76 years among females (95% CI: 1.51, 4.01); associations were strongest among NHW and NHA adults, and Hispanic males. Targeting upstream sources of structural disadvantage among racial/ethnic minority groups, in conjunction with improvements in income and education, may promote healthy aging in these populations.

2.
Arch Rehabil Res Clin Transl ; 6(2): 100333, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39006113

ABSTRACT

Chronic low back pain (CLBP) is a debilitating, painful, and costly condition. Implantable neuromuscular electrical stimulation targeting the multifidus musculature is growing as a non-pharmacologic option for patients with recalcitrant nociceptive mechanical CLBP who have failed conservative treatments (including medications and physical therapy) and for whom surgery is not indicated. Properly selecting patients who meet specific criteria (based on historical results from randomized controlled trials), who diligently adhere to implant usage and precisely implement neuromuscular rehabilitation, improve success of significant functional recovery, as well as pain medication reductions. Patients with nociceptive mechanical CLBP who underwent implanted multifidus neurostimulation have been treated by physicians and rehabilitation specialists who have honed their experience working with multifidus neurostimulation. They have collaborated on consensus and evidence-driven guidelines to improve quality outcomes and to assist providers when encountering patients with this device. Physicians and physical therapists together provide precision patient-centric medical management with quality neuromuscular rehabilitation to encourage patients to be experts of both their implants and quality spine motion to help override long-standing multifidus dysfunction related to their CLBP.

3.
Dig Dis Sci ; 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-39014101

ABSTRACT

BACKGROUND AND AIMS: Pre-liver transplant (LT) functional status is an important determinant of prognosis post LT. There is insufficient data on how functional status affects outcomes of transplant recipients based on the specific etiology of liver disease. We stratified LT recipients by etiology of liver disease to evaluate the effects of functional status on post-LT prognosis in each subgroup. METHODS: 2005-2019 United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) was used to select patients with liver transplant. A total of 14,290 patients were included in the analysis. These patients were stratified by functional status according to Karnofsky Performance Scale (KPS) score: no assistance, some assistance, or total assistance. They were then further divided into six diagnosis categories: metabolic dysfunction-associated steatotic liver disease (MASLD), hereditary disorders, hepatitis C, hepatitis B, autoimmune disease (AID), and alcoholic liver disease (ALD). Primary endpoints included all-cause mortality and graft failure, while secondary endpoints included organ-specific causes of death. Those under the age of 18 and those with non-whole liver or prior liver transplantation were excluded. RESULTS: Patients with MASLD requiring some assistance (aHR: 1.57, 95% CI 1.03-2.39, p = 0.04) and those requiring total assistance (aHR: 2.32, 95% CI 1.48-3.64, p < 0.001) had higher incidences of graft failure compared to those requiring no assistance. Those with MASLD requiring total assistance had a higher all-cause mortality rate than those needing no assistance (aHR: 1.62, 95% CI 1.38-1.89, p < 0.001). Patients with hereditary causes of liver disease showed a lower incidence of all-cause mortality in recipients needing some assistance compared with those needing no assistance (aHR: 0.52, 95% CI 0.34-0.80, p = 0.003). LT recipients with hepatitis C, AID, and ALD all showed higher incidences of all-cause mortality in the total assistance cohort when compared to the no assistance cohort. For the secondary endpoints of specific cause of death, transplant recipients with MASLD needing total assistance had higher rates of death due to general cardiac causes, graft rejection, general infectious causes, sepsis, general renal causes, and general respiratory causes. CONCLUSION: Patients with MASLD cirrhosis demonstrated the worst overall outcomes, suggesting that this population may be particularly vulnerable. Poor functional status in patients with end-stage liver disease from hepatitis B or hereditary disease was not associated with a significantly increased rate of adverse outcomes, suggesting that the KPS score may not be broadly applicable to all patients awaiting LT.

4.
bioRxiv ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38979380

ABSTRACT

Integrin α5ß1 is crucial for cell attachment and migration in development and tissue regeneration, and α5ß1 binding proteins could have considerable utility in regenerative medicine and next-generation therapeutics. We use computational protein design to create de novo α5ß1-specific modulating miniprotein binders, called NeoNectins, that bind to and stabilize the open state of α5ß1. When immobilized onto titanium surfaces and throughout 3D hydrogels, the NeoNectins outperform native fibronectin and RGD peptide in enhancing cell attachment and spreading, and NeoNectin-grafted titanium implants outperformed fibronectin and RGD-grafted implants in animal models in promoting tissue integration and bone growth. NeoNectins should be broadly applicable for tissue engineering and biomedicine. One-Sentence Summary: A de novo-designed fibronectin substitute, NeoNectin, is specific for integrin α5ß1 and can be incorporated into biomaterials for regenerative medicine.

6.
J Occup Environ Med ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38955796

ABSTRACT

OBJECTIVE: Determine whether volunteer firefighters in Florida are at increased odds of developing cancer compared to non-firefighters. METHODS: A case-control study design was implemented to assess the odds of developing cancer among male and female volunteer firefighters in Florida. Gender-specific age and calendar year-adjusted odds ratios (aOR) and 95% confidence intervals (95%CI) were estimated. RESULTS: Male volunteer firefighters were at increased odds for developing prostate (aOR = 1.26; 95%CI;[1.10- 1.44]) and male genital cancers combined (1.22;[1.07-1.39]), while reduced odds for endocrine cancer (0.41;[0.17-1.00]), and all leukemias (0.55;[0.35-0.86]), including lymphocytic (0.48;[0.24-0.97]); and chronic lymphocytic (0.40;[0.17-0.97]) leukemias. Female volunteer firefighters were at increased odds of developing of kidney cancer (2.51;[1.29-4.91]). CONCLUSIONS: Male volunteer firefighters are at increased odds for prostate and overall male genital cancers, while female volunteers are increased odds of kidney cancer.

7.
BMC Med ; 22(1): 296, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39020355

ABSTRACT

BACKGROUND: Sexually transmitted infections (STIs) pose a significant global public health challenge. Early diagnosis and treatment reduce STI transmission, but rely on recognising symptoms and care-seeking behaviour of the individual. Digital health software that distinguishes STI skin conditions could improve health-seeking behaviour. We developed and evaluated a deep learning model to differentiate STIs from non-STIs based on clinical images and symptoms. METHODS: We used 4913 clinical images of genital lesions and metadata from the Melbourne Sexual Health Centre collected during 2010-2023. We developed two binary classification models to distinguish STIs from non-STIs: (1) a convolutional neural network (CNN) using images only and (2) an integrated model combining both CNN and fully connected neural network (FCN) using images and metadata. We evaluated the model performance by the area under the ROC curve (AUC) and assessed metadata contributions to the Image-only model. RESULTS: Our study included 1583 STI and 3330 non-STI images. Common STI diagnoses were syphilis (34.6%), genital warts (24.5%) and herpes (19.4%), while most non-STIs (80.3%) were conditions such as dermatitis, lichen sclerosis and balanitis. In both STI and non-STI groups, the most frequently observed groups were 25-34 years (48.6% and 38.2%, respectively) and heterosexual males (60.3% and 45.9%, respectively). The Image-only model showed a reasonable performance with an AUC of 0.859 (SD 0.013). The Image + Metadata model achieved a significantly higher AUC of 0.893 (SD 0.018) compared to the Image-only model (p < 0.01). Out of 21 metadata, the integration of demographic and dermatological metadata led to the most significant improvement in model performance, increasing AUC by 6.7% compared to the baseline Image-only model. CONCLUSIONS: The Image + Metadata model outperformed the Image-only model in distinguishing STIs from other skin conditions. Using it as a screening tool in a clinical setting may require further development and evaluation with larger datasets.


Subject(s)
Metadata , Sexually Transmitted Diseases , Humans , Sexually Transmitted Diseases/diagnosis , Male , Female , Adult , Artificial Intelligence , Middle Aged , Neural Networks, Computer , Young Adult , Mass Screening/methods , Skin Diseases/diagnosis , Deep Learning
8.
Nat Commun ; 15(1): 5544, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956015

ABSTRACT

Goal-directed tasks involve acquiring an internal model, known as a predictive map, of relevant stimuli and associated outcomes to guide behavior. Here, we identified neural signatures of a predictive map of task behavior in perirhinal cortex (Prh). Mice learned to perform a tactile working memory task by classifying sequential whisker stimuli over multiple training stages. Chronic two-photon calcium imaging, population analysis, and computational modeling revealed that Prh encodes stimulus features as sensory prediction errors. Prh forms stable stimulus-outcome associations that can progressively be decoded earlier in the trial as training advances and that generalize as animals learn new contingencies. Stimulus-outcome associations are linked to prospective network activity encoding possible expected outcomes. This link is mediated by cholinergic signaling to guide task performance, demonstrated by acetylcholine imaging and systemic pharmacological perturbation. We propose that Prh combines error-driven and map-like properties to acquire a predictive map of learned task behavior.


Subject(s)
Memory, Short-Term , Perirhinal Cortex , Animals , Mice , Perirhinal Cortex/physiology , Memory, Short-Term/physiology , Male , Learning/physiology , Mice, Inbred C57BL , Vibrissae/physiology , Acetylcholine/metabolism , Behavior, Animal/physiology , Female
9.
Sci Rep ; 14(1): 14917, 2024 06 28.
Article in English | MEDLINE | ID: mdl-38942819

ABSTRACT

In tuberculosis (TB), chest radiography (CXR) patterns are highly variable, mimicking pneumonia and many other diseases. This study aims to evaluate the efficacy of Google teachable machine, a deep neural network-based image classification tool, to develop algorithm for predicting TB probability of CXRs. The training dataset included 348 TB CXRs and 3806 normal CXRs for training TB detection. We also collected 1150 abnormal CXRs and 627 normal CXRs for training abnormality detection. For external validation, we collected 250 CXRs from our hospital. We also compared the accuracy of the algorithm to five pulmonologists and radiological reports. In external validation, the AI algorithm showed areas under the curve (AUC) of 0.951 and 0.975 in validation dataset 1 and 2. The accuracy of the pulmonologists on validation dataset 2 showed AUC range of 0.936-0.995. When abnormal CXRs other than TB were added, AUC decreased in both human readers (0.843-0.888) and AI algorithm (0.828). When combine human readers with AI algorithm, the AUC further increased to 0.862-0.885. The TB CXR AI algorithm developed by using Google teachable machine in this study is effective, with the accuracy close to experienced clinical physicians, and may be helpful for detecting tuberculosis by CXR.


Subject(s)
Algorithms , Deep Learning , Radiography, Thoracic , Tuberculosis, Pulmonary , Humans , Tuberculosis, Pulmonary/diagnostic imaging , Tuberculosis, Pulmonary/diagnosis , Radiography, Thoracic/methods , Female , Male , Middle Aged , Adult , Area Under Curve
10.
Front Endocrinol (Lausanne) ; 15: 1365260, 2024.
Article in English | MEDLINE | ID: mdl-38887270

ABSTRACT

Anti-Müllerian hormone (AMH) is a key paracrine/autocrine factor regulating folliculogenesis in the postnatal ovary. As antral follicles mature to the preovulatory stage, AMH production tends to be limited to cumulus cells. Therefore, the present study investigated the role of cumulus cell-derived AMH in supporting maturation and competence of the enclosed oocyte. Cumulus-oocyte complexes (COCs) were isolated from antral follicles of rhesus macaque ovaries for in vitro maturation with or without AMH depletion. Oocyte meiotic status and embryo cleavage after in vitro fertilization were assessed. In vitro maturation with AMH depletion was also performed using COCs from antral follicles of human ovarian tissue. Oocyte maturation and morphology were evaluated. The direct AMH action on mural granulosa cells of the preovulatory follicle was further assessed using human granulosa cells cultured with or without AMH supplementation. More macaque COCs produced metaphase II oocytes with AMH depletion than those of the control culture. However, preimplantation embryonic development after in vitro fertilization was comparable between oocytes derived from COCs cultured with AMH depletion and controls. Oocytes resumed meiosis in human COCs cultured with AMH depletion and exhibited a typical spindle structure. The confluency and cell number decreased in granulosa cells cultured with AMH supplementation relative to the control culture. AMH treatment did not induce cell death in cultured human granulosa cells. Data suggest that reduced AMH action in COCs could be beneficial for oocyte maturation. Cumulus cell-derived AMH is not essential for supporting oocyte competence or mural granulosa cell viability.


Subject(s)
Anti-Mullerian Hormone , Cumulus Cells , In Vitro Oocyte Maturation Techniques , Macaca mulatta , Oocytes , Anti-Mullerian Hormone/metabolism , Oocytes/metabolism , Oocytes/cytology , Oocytes/drug effects , Female , Cumulus Cells/metabolism , Cumulus Cells/cytology , Cumulus Cells/drug effects , Animals , Humans , In Vitro Oocyte Maturation Techniques/methods , Oogenesis/physiology , Oogenesis/drug effects , Cells, Cultured , Fertilization in Vitro/methods , Meiosis/physiology , Meiosis/drug effects , Granulosa Cells/metabolism , Granulosa Cells/cytology , Ovarian Follicle/metabolism , Ovarian Follicle/cytology , Ovarian Follicle/physiology , Embryonic Development/physiology
11.
J Bone Miner Res ; 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38861422

ABSTRACT

Randomized trials have not been performed, and may never be, to determine if osteoporosis treatment prevents hip fracture in men. Addressing that evidence gap, we analyzed data from an observational study of new hip fractures in a large integrated healthcare system to compare the reduction in hip fractures associated with standard-of-care osteoporosis treatment in men versus women. Sampling from 271 389 patients age ≥ 65 who had a hip-containing computed tomography scan during care between 2005-2018, we selected all who subsequently had a first hip fracture (cases) after the CT scan (start of observation) and a sex-matched equal number of randomly selected patients. From those, we analyzed all who tested positive for osteoporosis (DXA-equivalent hip bone mineral density T-score ≤ -2.5, measured from the CT scan using VirtuOst). We defined "treated" as at least six months of any osteoporosis medication by prescription fill data during follow up; "not-treated" was no prescription fill. Sex-specific odds ratios of hip fracture for treated versus not-treated patients were calculated by logistic regression; adjustments included age, BMD T-score, a BMD-treatment interaction, body mass index, race/ethnicity, and seven baseline clinical risk factors. At two-year follow-up, 33.9% of the women (750/2211 patients) and 24.0% of the men (175/728 patients) were treated, primarily with alendronate; 51.3% and 66.3%, respectively, were not-treated; and 721 and 269, respectively, had a first hip fracture since the CT scan. Odds ratio of hip fracture for treated versus not-treated was 0.26 (95% confidence interval: 0.21-0.33) for women and 0.21 (0.13-0.34) for men; the ratio of these odds ratios (men:women) was 0.81 (0.47-1.37), indicating no significant sex effect. Various sensitivity and stratified analyses confirmed these trends, including results at five-year follow-up. Given these results and considering the relevant literature, we conclude that osteoporosis treatment prevents hip fracture similarly in both sexes.


Much evidence suggests that osteoporosis treatment should prevent hip fracture similarly in both sexes. However, because of their expense, randomized clinical trials to demonstrate that definitively have not been performed and may never be. As a result, osteoporosis testing and treatment is not as widely adopted for men as it is for women. Addressing that evidence gap, we analyzed data from over 250 000 patients in the Kaiser Permanente healthcare system in Southern California. Sampling a subset of all patients over a 13-year period who had had a computed tomography (CT or CAT) scan as part of their medical care for any reason, we measured bone mineral density from the CT scans to identify all patients who had osteoporosis at the hip and then used data from the electronic health records to determine statistically the risk of a future hip fracture for those who were treated for osteoporosis versus those who were not treated. We found that the reduction in risk of hip fracture associated with treatment did not differ between the sexes. These results demonstrate that treating osteoporosis in patients at high risk of hip fracture should reduce the risk of hip fracture similarly in both sexes.

12.
J Registry Manag ; 51(1): 41-48, 2024.
Article in English | MEDLINE | ID: mdl-38881985

ABSTRACT

Background: Hospital electronic medical record (EMR) systems are becoming increasingly integrated for management of patient data, especially given recent policy changes issued by the Centers for Medicaid and Medicare Services. In addition to data management, these data provide evidence for patient-centered outcomes research for a range of diseases, including cancer. Integrating EMR patient data with existing disease registries strengthens all essential components for assuring optimal health outcomes. Objectives: To identify the mechanisms for extracting, linking, and processing hospital EMR data with the Florida Cancer Data System (FCDS); and to assess the completeness of existing registry treatment data as well as the potential for data enhancement. Methods: A partnership among the Florida Department of Health, FCDS, and a large Florida hospital system was established to develop methods for hospital EMR extraction and transmission. Records for admission years between 2007 and 2010 were extracted using ICD-9-CM codes as the trigger and were linked with the cancer registry for patients with invasive cancers of the breast. Results: A total of 11,506 unique patients were linked with a total of 12,804 unique breast tumors. Evaluation of existing registry treatment data against the hospital EMR produced a total of 5% of registry records with updated surgery information, 1% of records with updated radiation information, and 7% of records updated with chemotherapy information. Enhancement of registry treatment information was particularly affected by the availability of chemotherapy medications data. Conclusion: Hospital EMR linkages to cancer disease registries is feasible but challenged by lack of standards for data collection, coding and transmission, comprehensive description of available data, and the exclusion of certain hospital datasets. The FCDS standard treatment data variables are highly robust and complete but can be enhanced by the addition of detailed chemotherapy regimens that are commonly used in patient centered outcomes research.


Subject(s)
Electronic Health Records , Medical Record Linkage , Registries , Humans , Pilot Projects , Florida/epidemiology , Female , Breast Neoplasms/epidemiology , Breast Neoplasms/therapy , Neoplasms/epidemiology , Neoplasms/therapy
13.
World J Urol ; 42(1): 375, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38872048

ABSTRACT

BACKGROUND: The International Prostate Symptom Score (IPSS) is a patient-reported measurement to assess the lower urinary tract symptoms of bladder outlet obstruction. Bladder outlet obstruction induces molecular and morphological alterations in the urothelium, suburothelium, detrusor smooth muscle cells, detrusor extracellular matrix, and nerves. We sought to analyze MRI-based radiomics features of the urinary bladder wall and their association with IPSS. METHOD: In this retrospective study, 87 patients who had pelvic MRI scans were identified. A biomarker discovery approach based on the optimal biomarker (OBM) method was used to extract features of the bladder wall from MR images, including morphological, intensity-based, and texture-based features, along with clinical variables. Mathematical models were created using subsets of features and evaluated based on their ability to discriminate between low and moderate-to-severe IPSS (less than 8 vs. equal to or greater than 8). RESULTS: Of the 7,666 features per patient, four highest-ranking optimal features were derived (all texture-based features), which provided a classification accuracy of 0.80 with a sensitivity, specificity, and area under the receiver operating characteristic curve of 0.81, 0.81, and 0.87, respectively. CONCLUSION: A highly independent set of urinary bladder wall features derived from MRI scans were able to discriminate between patients with low vs. moderate-to-severe IPSS with accuracy of 80%. Such differences in MRI-based properties of the bladder wall in patients with varying IPSS's might reflect differences in underlying molecular and morphological alterations that occur in the setting of chronic bladder outlet obstruction.


Subject(s)
Magnetic Resonance Imaging , Severity of Illness Index , Urinary Bladder Neck Obstruction , Urinary Bladder , Humans , Retrospective Studies , Urinary Bladder/diagnostic imaging , Urinary Bladder/pathology , Male , Urinary Bladder Neck Obstruction/diagnostic imaging , Middle Aged , Aged , Lower Urinary Tract Symptoms/diagnostic imaging , Lower Urinary Tract Symptoms/etiology , Symptom Assessment , Radiomics
14.
bioRxiv ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38903095

ABSTRACT

Sensory hair cells of the inner ear utilize specialized ribbon synapses to transmit sensory stimuli to the central nervous system. This sensory transmission necessitates rapid and sustained neurotransmitter release, which relies on a large pool of synaptic vesicles at the hair-cell presynapse. Work in neurons has shown that kinesin motor proteins traffic synaptic material along microtubules to the presynapse, but how new synaptic material reaches the presynapse in hair cells is not known. We show that the kinesin motor protein Kif1a and an intact microtubule network are necessary to enrich synaptic vesicles at the presynapse in hair cells. We use genetics and pharmacology to disrupt Kif1a function and impair microtubule networks in hair cells of the zebrafish lateral-line system. We find that these manipulations decrease synaptic-vesicle populations at the presynapse in hair cells. Using electron microscopy, along with in vivo calcium imaging and electrophysiology, we show that a diminished supply of synaptic vesicles adversely affects ribbon-synapse function. Kif1a mutants exhibit dramatic reductions in spontaneous vesicle release and evoked postsynaptic calcium responses. Additionally, we find that kif1a mutants exhibit impaired rheotaxis, a behavior reliant on the ability of hair cells in the lateral line to respond to sustained flow stimuli. Overall, our results demonstrate that Kif1a-based microtubule transport is critical to enrich synaptic vesicles at the active zone in hair cells, a process that is vital for proper ribbon-synapse function.

15.
Article in English | MEDLINE | ID: mdl-38928988

ABSTRACT

Studies examining occupational exposures and cancer risk frequently report mixed findings; it is thus imperative for researchers to synthesize study results and identify any potential sources that explain such variabilities in study findings. However, when synthesizing study results using meta-analytic techniques, researchers often encounter a number of practical and methodological challenges. These challenges include (1) an incomparability of effect size measures due to large variations in research methodology; (2) a violation of the independence assumption for meta-analysis; (3) a violation of the normality assumption of effect size measures; and (4) a variation in cancer definitions across studies and changes in coding standards over time. In this paper, we first demonstrate these challenges by providing examples from a real dataset collected for a large meta-analysis project that synthesizes cancer mortality and incidence rates among firefighters. We summarize how each of these challenges has been handled in our meta-analysis. We conclude this paper by providing practical guidelines for handling challenges when synthesizing study findings from occupational cancer literature.


Subject(s)
Meta-Analysis as Topic , Neoplasms , Occupational Exposure , Humans , Neoplasms/epidemiology , Occupational Diseases/epidemiology , Firefighters , Research Design , Incidence
16.
Br J Haematol ; 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802107

ABSTRACT

The Canadian Cancer Trials Group (CCTG) LY.17 is an ongoing multi-arm randomized phase II trial evaluating novel salvage therapies compared with R-GDP (rituximab, gemcitabine, dexamethasone and cisplatin) in autologous stem cell transplantation (ASCT)-eligible patients with relapsed/refractory diffuse large B-cell lymphoma (RR-DLBCL). This component of the LY.17 trial evaluated a dose-intensive chemotherapy approach using a single cycle of inpatient R-DICEP (rituximab, dose-intensive cyclophosphamide, etoposide and cisplatin) to achieve both lymphoma response and stem cell mobilization, shortening time to ASCT. This report is the result of the protocol-specified second interim analysis of the 67 patients who were randomized to either 1 cycle of R-DICEP or to 3 cycles of R-GDP. The overall response rate (ORR) was 65.6% for R-DICEP and 48.6% for R-GDP. The ASCT rate was 71.9% versus 54.3%, and 1-year progression-free survival rate was 42% versus 32%, respectively, for R-DICEP versus R-GDP. Although the improvement in ORR for R-DICEP versus R-GDP exceeded the pre-specified 10% threshold to proceed to full accrual of 64 patients/arm, higher rates of grade 3-5 toxicities, and the need for hospitalization led to the decision to stop this arm of the study. CCTG LY.17 will continue to evaluate different salvage regimens that incorporate novel agents.

17.
Heliyon ; 10(10): e31354, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38807877

ABSTRACT

Objective: To perform a geospatial analysis of food insecurity in a rural county known to have poor health outcomes and assess the effect of the COVID-19 pandemic. Methods: In 2020, we mailed a comprehensive cross-sectional survey to all households in Sullivan County, a rural county with the second-worst health outcomes among all counties in New York State. Surveys of households included validated food insecurity screening questions. Questions were asked in reference to 2019, prior to the pandemic, and for 2020, in the first year of the pandemic. Respondents also responded to demographic questions. Raking adjustments were performed using age, sex, race/ethnicity, and health insurance strata to mitigate non-response bias. To identify significant hotspots of food insecurity within the county, we also performed geospatial analysis. Findings: From the 28,284 households surveyed, 20% of households responded. Of 4725 survey respondents, 26% of households reported experiencing food insecurity in 2019, and in 2020, this proportion increased to 35%. In 2020, 58% of Black and Hispanic households reported experiencing food insecurity. Food insecurity in 2020 was also present in 58% of unmarried households with children and in 64% of households insured by Medicaid. The geospatial analyses revealed that hotspots of food insecurity were primarily located in or near more urban areas of the rural county. Conclusions: Our countywide health survey in a high-risk rural county identified significant increases of food insecurity in the first year of the COVID-19 pandemic, despite national statistics reporting a stable rate. Responses to future crises should include targeted interventions to bolster food security among vulnerable rural populations.

18.
bioRxiv ; 2024 May 02.
Article in English | MEDLINE | ID: mdl-38746206

ABSTRACT

While there has been progress in the de novo design of small globular miniproteins (50-65 residues) to bind to primarily concave regions of a target protein surface, computational design of minibinders to convex binding sites remains an outstanding challenge due to low level of overall shape complementarity. Here, we describe a general approach to generate computationally designed proteins which bind to convex target sites that employ geometrically matching concave scaffolds. We used this approach to design proteins binding to TGFßRII, CTLA-4 and PD-L1 which following experimental optimization have low nanomolar to picomolar affinities and potent biological activity. Co-crystal structures of the TGFßRII and CTLA-4 binders in complex with the receptors are in close agreement with the design models. Our approach provides a general route to generating very high affinity binders to convex protein target sites.

19.
Orthop Rev (Pavia) ; 16: 116960, 2024.
Article in English | MEDLINE | ID: mdl-38699080

ABSTRACT

Background: Low back pain (LBP) is a common problem which can affect balance and, in turn, increase fall risk. The aim of this investigation was to evaluate the impact of a Sacroiliac Belt (SB) on balance and stability in patients with LBP. Methods: Subjects with LBP and without LBP ("Asymptomatic") were enrolled. Baseline balance was assessed using the Berg Balance Scale. In a counterbalanced crossover design, LBP and Asymptomatic subjects were randomized to one of two groups: 1) start with wearing the SB (Serola Biomechanics, Inc.) followed by not wearing the SB or 2) start without wearing the SB followed by wearing the SB. For subjects in both groups, dynamic balance was then assessed using the Star Excursion Balance Test (SEBT) with each leg planted. Results: Baseline balance was worse in LBP subjects (Berg 51/56) than Asymptomatic subjects (Berg 56/56) (p<0.01). SB significantly improved SEBT performance in LBP subjects regardless of which leg was planted (p<0.01). SB positively impacted Asymptomatic subjects' SEBT performance with the left leg planted (p=0.0002). Conclusion: The Serola Sacroiliac Belt positively impacted dynamic balance for subjects with low back pain. Further research is needed to examine additional interventions and outcomes related to balance in patients with back pain, and to elucidate the mechanisms behind improvements in balance related to sacroiliac belt utilization.

20.
J Am Vet Med Assoc ; 262(8): 1-5, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-38701838

ABSTRACT

OBJECTIVE: To determine the value veterinary students place on nonpecuniary job benefits related to working arrangements. SAMPLE: 381 companion animal-focused veterinary students at 14 US veterinary colleges. METHODS: We employed a survey with a choice-based conjoint experiment. The experimental data were analyzed with a random parameter logit model, from which willingness to accept was calculated. RESULTS: The results indicated that students would prefer working 4 days a week and closer to 40 hours per week, with 13 days of paid time off. Flexible working arrangements were valued from approximately $1,500 to $3,400, depending on the attribute being analyzed. Paid time off was most highly valued. CLINICAL RELEVANCE: These results will help employers better identify the current preferences of soon-to-be associate veterinarians and can match job offer/working arrangements to enhance recruitment and retention within veterinary practices.


Subject(s)
Salaries and Fringe Benefits , Students , Salaries and Fringe Benefits/statistics & numerical data , Humans , Students/psychology , Female , Male , Education, Veterinary/economics , Veterinarians/psychology , Career Choice , Adult , Surveys and Questionnaires , Young Adult , Data Collection , United States , Animals
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