DART.2: bidirectional synaptic pharmacology with thousandfold cellular specificity.

Precision pharmacology aims to manipulate specific cellular interactions within complex tissues. In this pursuit, we introduce DART.2 (drug acutely restricted by tethering), a second-generation cell-specific pharmacology technology. The core advance is optimized cellular specificity-up to 3,000-fold in 15 min-enabling the targeted delivery of even epileptogenic drugs without off-target effects. Additionally, we introduce brain-wide dosing methods as an alternative to local cannulation and tracer reagents for brain-wide dose quantification. We describe four pharmaceuticals-two that antagonize excitatory and inhibitory postsynaptic receptors, and two that allosterically potentiate these receptors. Their versatility is showcased across multiple mouse-brain regions, including cerebellum, striatum, visual cortex and retina. Finally, in the ventral tegmental area, we find that blocking inhibitory inputs to dopamine neurons accelerates locomotion, contrasting with previous optogenetic and pharmacological findings. Beyond enabling the bidirectional perturbation of chemical synapses, these reagents offer intersectional precision-between genetically defined postsynaptic cells and neurotransmitter-defined presynaptic partners.

A group-based intervention for diabetes-related emotional distress among emerging adults with type 1 diabetes: A pilot study.

AIMS: To assess diabetes-related emotional distress (DD) in emerging adults with type 1 diabetes (T1D) and assess a group-based intervention's impact. METHODS: To investigate DD we used data from the Problem Areas in Diabetes Questionnaire comprising 20 items (PAID-20). Furthermore, changes in the WHO Well-Being Index comprising five items (WHO-5) and glycated haemoglobin (HbA1c) were analysed. The intervention was evaluated using follow-up data from the emerging adults who participated. RESULTS: From 2021 to 2023, we screened 180 emerging adults using PAID-20. DD (PAID-20≥30) was prevalent in 25.0 % (95 % CI 18.9; 32.0 %), and associated with the female sex, higher HbA1c and WHO-5 < 50. Continuous subcutaneous insulin infusion at baseline was associated with PAID-20<30. 21 individuals attended a group-based intervention. At one-week follow up PAID-20 was reduced (29.1 ± 15.4 vs. 41.3 ± 12.1 at baseline, p = 0.003), and at nine-twelve months' follow-up HbA1c was reduced (59.3 ± 15.3 mmol/mol vs. 68.0 ± 17.4 mmol/mol at baseline, p = 0.012). CONCLUSIONS: This pilot study demonstrated that 25 % of the investigated emerging adults with T1D experienced DD (PAID-20≥30) associated with four clinical factors. We found a reduction in HbA1c and a short-term reduction in PAID-20 following the group-based intervention.

'Walk Buds': A walking intervention to increase physical activity, physical fitness, and emotional wellbeing, in 9-13 year old children with intellectual disabilities. Results of a clustered randomised feasibility trial.

BACKGROUND: Children with intellectual disability are less physically active and more sedentary than typically developing peers. To date no studies have tested the feasibility of a school-based walking intervention for children with Intellectual Disability. METHOD: A clustered randomised controlled trial (cRCT), with an embedded process evaluation, was used to test the feasibility of a school-based walking intervention. Eight schools (n = 161 pupils aged 9-13 years) were randomised into either an intervention arm or an 'exercise as usual' arm. Measures included physical activity, physical fitness and emotional wellbeing. Baseline and 3-month follow-up data were collected. RESULTS: The 'Walk Buds' intervention was found to be acceptable to teaching staff and pupils, with an uptake rate of the walking sessions offered of 84%. CONCLUSION: A number of challenges were experienced, relating to the COVID-19 pandemic, and difficulties collecting accelerometer data. Barriers, facilitators and required changes identified through the mixed methods process evaluation are discussed.

Fear attenuation collaborations to optimize translation.

Here, we describe the efforts we dedicated to the challenge of modifying entrenched emotionally laden memories. In recent years, through a number of collaborations and using a combination of behavioral, molecular, and computational approaches, we: (a) developed novel approaches to fear attenuation that engage mechanisms that differ from those engaged during extinction (Monfils), (b) examined whether our approaches can generalize to other reinforcers (Lee, Gonzales, Chaudhri, Cofresi, and Monfils), (c) derived principled explanations for the differential outcomes of our approaches (Niv, Gershman, Song, and Monfils), (d) developed better assessment metrics to evaluate outcome success (Shumake and Monfils), (e) identified biomarkers that can explain significant variance in our outcomes of interest (Shumake and Monfils), and (f) developed better basic research assays and translated efforts to the clinic (Smits, Telch, Otto, Shumake, and Monfils). We briefly highlight each of these milestones and conclude with final remarks and extracted principles. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

How Does the University Environment Relate to Student's Physical Activity Patterns in Ireland.

BACKGROUND: Identifying factors related to physical activity in university students can aid the development of health promotion interventions, but there is limited research regarding the influence of university environments. This study examined the relationship between level of provision for university environments that aim to promote physical activity and self-reported physical activity patterns of students. METHODS: An environmental audit tool was completed by universities (n = 28) on the island of Ireland to acquire information about physical activity opportunities, resources, and supports offered. Students (N = 6951; 50.7% male; 21.51 [5.55] y) completed an online survey, providing responses about their active transport and recreational physical activity behaviors. Binary logistic regressions were used to examine the associations between environmental factors that support physical activity and clustered physical activity patterns, while controlling for gender, age, and university size. RESULTS: Universities with a high provision for organizational structures and internal partnerships, indoor facilities, and sport clubs increase the odds of their students having more active physical activity patterns. Increased provision of investment and personnel was seen to have a mixed relationship with students' physical activity engagement, highlighting the need to understand where resources are needed and not just increase them. CONCLUSIONS: It is important for universities to have adequate organizational structures with internal partnerships to understand how resources can be maximized to support physical activity engagement across the whole student population. University campuses hold the potential for increasing student engagement in physical activity, and these findings can help inform campus-wide initiatives that foster active student populations for improving overall long-term health.

Carbon Dioxide Reactivity Differentially Predicts Fear Expression After Extinction and Retrieval-Extinction in Rats.

Background: Cues present during a traumatic event may result in persistent fear responses. These responses can be attenuated through extinction learning, a core component of exposure therapy. Exposure/extinction is effective for some people, but not all. We recently demonstrated that carbon dioxide (CO2) reactivity predicts fear extinction memory and orexin activation and that orexin activation predicts fear extinction memory, which suggests that a CO2 challenge may enable identification of whether an individual is a good candidate for an extinction-based approach. Another method to attenuate conditioned responses, retrieval-extinction, renders the original associative memory labile via distinct neural mechanisms. The purpose of the current study was to examine whether we could replicate previous findings that retrieval-extinction is more effective than extinction at preventing the return of fear and that CO2 reactivity predicts fear memory after extinction. We also examined whether CO2 reactivity predicts fear memory after retrieval-extinction. Methods: Male rats first underwent a CO2 challenge and fear conditioning and were assigned to receive either standard extinction (n = 28) or retrieval-extinction (n = 28). Then, they underwent a long-term memory (LTM) test and a reinstatement test. Results: We found that retrieval-extinction resulted in lower freezing during extinction, LTM, and reinstatement than standard extinction. Using the best subset approach to linear regression, we found that CO2 reactivity predicted LTM after extinction and also predicted LTM after retrieval-extinction, although to a lesser degree. Conclusions: CO2 reactivity could be used as a screening tool to determine whether an individual may be a good candidate for an extinction-based therapeutic approach.

Extinction learning underlies exposure therapy, a treatment for anxiety disorders. However, not everyone benefits from exposure therapy, highlighting the need in developing approaches that may help predict which individuals will respond. We tested whether extinction or an alternative treatment called retrieval-extinction would be more effective at reducing conditioned fear responses in rats and whether the response to a carbon dioxide (CO₂) challenge would predict treatment response. We found that retrieval-extinction was more effective at reducing fear, and CO₂ reactivity was better at predicting the response to extinction. These findings could help improve treatment strategies for anxiety disorders.

Conspecific interactions predict social transmission of fear in female rats.

Social transmission of fear occurs in a subset of individuals, where an Observer displays a fear response to a previously neutral stimulus after witnessing or interacting with a conspecific Demonstrator during memory retrieval. The conditions under which fear can be acquired socially in rats have received attention in recent years, and suggest that social factors modulate social transmission of information. We previously found that one such factor, social rank, impacts fear conditioning by proxy in male rats. Here, we aimed to investigate whether social roles as determined by nape contacts in females, might also have an influence on social transmission of fear. In-line with previous findings in males, we found that social interactions in the home cage can provide insight into the social relationship between female rats and that these relationships predict the degree of fear acquired by-proxy. These results suggest that play behavior affects the social transfer/transmission of information in female rats.

Effects of group size on movement patterns and clustering dynamics in rats.

Environment is a determining factor that can facilitate or hinder social interactions. A precursor to meaningfully engaging with conspecifics is being exposed to opportunistic encounters with others. Increasing the number of individuals in a given space (thus increasing density) would, statistically speaking, increase the likelihood of accidental encounters. This might have consequences on the formation of social networks-an idea that has not reliably been explored. If true, we would expect that increasing density would lead to an increase in the number and the duration of 'clusters' of animals. Here, we examined whether varying the number of rats in an open field environment differentially affected their movement dynamics or their propensity to aggregate into clusters and, if so, whether such effects are dependent solely on statistical factors due to increases in density, the potential for actively-sought social interactions, or both. We found that the number of rats in an environment impacts ambulation speed, distance traveled, cluster formation and approaches, and that number and duration of clusters are highly dependent on the propensity for the rats to engage in social interactions.

The International Olympic Committee framework on fairness, inclusion and nondiscrimination on the basis of gender identity and sex variations does not protect fairness for female athletes.

The International Olympic Committee (IOC) recently published a framework on fairness, inclusion, and nondiscrimination on the basis of gender identity and sex variations. Although we appreciate the IOC's recognition of the role of sports science and medicine in policy development, we disagree with the assertion that the IOC framework is consistent with existing scientific and medical evidence and question its recommendations for implementation. Testosterone exposure during male development results in physical differences between male and female bodies; this process underpins male athletic advantage in muscle mass, strength and power, and endurance and aerobic capacity. The IOC's "no presumption of advantage" principle disregards this reality. Studies show that transgender women (male-born individuals who identify as women) with suppressed testosterone retain muscle mass, strength, and other physical advantages compared to females; male performance advantage cannot be eliminated with testosterone suppression. The IOC's concept of "meaningful competition" is flawed because fairness of category does not hinge on closely matched performances. The female category ensures fair competition for female athletes by excluding male advantages. Case-by-case testing for transgender women may lead to stigmatization and cannot be robustly managed in practice. We argue that eligibility criteria for female competition must consider male development rather than relying on current testosterone levels. Female athletes should be recognized as the key stakeholders in the consultation and decision-making processes. We urge the IOC to reevaluate the recommendations of their Framework to include a comprehensive understanding of the biological advantages of male development to ensure fairness and safety in female sports.

Feedback System Analysis of a Multicomponent Intervention on Dyads of Home-Dwelling Persons With Dementia and Their Caregivers: Results From the LIVE@Home.Path Trial.

Background and Objectives: Proper symptom management, informal caregiver support, and service innovation are required to reduce dementia care burden. The objective of this study is to investigate the effect of the multicomponent LIVE (Learning, Innovation, Volunteering, Empowerment) intervention on caregiver experience of the self-perceived care situation, coordinator performance, and informal care time. Research Design and Methods: We conducted a 24-month multicomponent, stepped-wedge randomized control trial including dyads of people ≥65 years with mild-to-moderate dementia with minimum weekly contact with their informal caregivers in Norway. The intervention was implemented by municipal coordinators over a 6-month period. This study investigates the first 6-month period (September 2019-March 2020) of the trial, due to the coronavirus disease 2019 (COVID-19) pandemic. Primary outcomes are changes in provision of informal care time assessed by Resource Utilization in Dementia Care (RUD) and informal caregiver experience assessed by the Clinical Global Impression of Change (CGIC). We use logistic regression and feedback system analysis to assess the reach of the multicomponent intervention. Results: A total of 280 dyads were included at baseline, mean age of the person with dementia was 81.8 years, and 62.5% were female. After 6 months, the feedback system analysis reveals that the caregivers randomized to the intervention period reported improved caregiver situation (CGIG-T: intervention 0.63 (SD 2.4) vs control -0.43 (SD 1.7), p < .01), even though informal care time for activities of daily living was not reduced (p = .31). Informal caregivers registered a positive change for the Learning, Innovation, and Empowerment components, while no change was found for Volunteer support. Discussion and Implications: Findings illustrate the usefulness of dementia care coordinators that provide regular follow-up. We also show that complex intervention studies benefit from applying feedback system analysis. Meeting the needs of persons with dementia and their caregivers is a complex process that requires coordinated input from health services and user communities. Clinical Trial Registration Number: NCT04043364.

Effectiveness of a health communication intervention on health literacy in the first year following kidney transplantation - A randomized controlled study.

OBJECTIVE: This study aimed to evaluate the effect of a new health communication intervention focusing on knowledge management skills on health literacy and medication adherence during the first year following kidney transplantation. METHODS: We randomized 195 patients during 2020-2021, to either intervention- or control group. Questionnaires were completed at baseline and at 12 months post-transplantation with a 12-month response rate of 84%. Health literacy was measured by the multidimensional Health Literacy Questionnaire (HLQ) instrument. Medication adherence was measured by the self-reported questionnaire (BAASIS©). RESULTS: Results showed that the intervention group had a significant increase in 2 HLQ domains compared to the control group capturing the "ability to appraise health information" Domain 5, (p-value = 0.002) and the "ability to navigate the healthcare system" Domain 7, (p-value <0.04). The effect sizes of SRM were 0.49 (Domain 5) and 0.33 (Domain 7). Medication adherence was comparable in the groups at any measure points. CONCLUSIONS: This study contributes to important knowledge about how a health communication intervention focusing on knowledge translation using motivational interviewing techniques positively strengthens health literacy in kidney transplant recipients. PRACTICAL IMPLICATIONS: Current patient education practice may benefit from focusing on knowledge translation in combination with motivational interview technique.

Impacts of a health literacy-informed intervention in people with chronic obstructive pulmonary disease (COPD) on hospitalization, health literacy, self-management, quality of life, and health costs - A randomized controlled trial.

OBJECTIVE: To compare the effect of motivational interviewing (MI) and tailored health literacy (HL) follow-up with usual care on hospitalization, costs, HL, self-management, Quality of life (QOL), and psychological stress in people with chronic obstructive pulmonary disease (COPD). METHODS: A RCT was undertaken in Norway between March 2018-December 2020 (n = 127). The control group (CG, n = 63) received usual care. The intervention group (IG, n = 64) received tailored HL follow-up from MI-trained COPD nurses with home visits for eight weeks and phone calls for four months after hospitalization. Primary outcomes were hospitalization at eight weeks, six months, and one year from baseline. The trial was registered with ClinicalTrials.gov (NCT03216603) and analysed per protocol. RESULTS: Compared with the IG, the CG had 2.8 higher odds (95% CI [1.3 to 5.8]) of hospitalization and higher hospital health costs (MD=€ -6230, 95% CI [-6510 to -5951]) and lower QALYs (MD=0.1, 95% CI [0.10 to 0.11]) that gives an ICER = - 62,300. The IG reported higher QOL, self-management, and HL (p = 0.02- to <0.01). CONCLUSION: MI-trained COPD nurses using tailored HL follow-up is cost-effective, reduces hospitalization, and increases QOL, HL, and self-care in COPD. PRACTICE IMPLICATION: Tailored HL follow-up is beneficial for individuals with COPD and the healthcare system.

Incidence of shoulder dystocia and risk factors for recurrence in the subsequent pregnancy-A historical register-based cohort study.

INTRODUCTION: Shoulder dystocia is a rare obstetric complication, and the risk of recurrence is important for planning future deliveries. MATERIAL AND METHODS: The objectives of our study were to estimate the incidence and risk factors for recurrence of shoulder dystocia and to identify women at high risk of recurrence in a subsequent vaginal delivery. The study design was a nationwide register-based study including data from the Danish Medical Birth Registry and National Patient Register in the period 2007-2017. Nulliparous women with a singleton fetus in cephalic presentation were included for analysis of risk factors in index and subsequent delivery. RESULTS: During the study period, 6002 cases of shoulder dystocia were reported with an overall incidence among women with vaginal delivery of 1.2%. Among 222 225 nulliparous women with vaginal births, shoulder dystocia complicated 2209 (1.0%) deliveries. A subsequent birth was registered in 1106 (50.1%) of the women with shoulder dystocia in index delivery of which 837 (77.8%) delivered vaginally. Recurrence of shoulder dystocia was reported in 60 (7.2%) with a six-fold increased risk compared with women without a prior history of shoulder dystocia (risk ratio [RR] 5.70, 95% confidence interval [CI]: 4.41 to 7.38; adjusted RR 3.06, 95% CI: 2.03 to 4.68). Low maternal height was a significant risk factor for recurrence of shoulder dystocia. In the subsequent delivery, significant risk factors for recurrence were birthweight >4000 g, positive fetal weight difference exceeding 250 g from index to subsequent delivery, stimulation with oxytocin and operative vaginal delivery. In the subsequent pregnancy following shoulder dystocia, women who underwent a planned cesarean (n = 176) were characterized by more advanced age and a higher prevalence of diabetes in the subsequent pregnancy. Furthermore, they had more often experienced operative vaginal delivery, severe perineal lacerations, and severe neonatal complications at the index delivery. CONCLUSIONS: The incidence of shoulder dystocia among nulliparous women with vaginal delivery was 1.0% with a 7.2% risk of recurrence in a population where about 50% had a subsequent birth and of these 78% had subsequent vaginal delivery. Important risk factors for recurrence were low maternal height, increase of birthweight ≥250 g from index to subsequent delivery and operative vaginal delivery.

Effectiveness of the Walking in ScHools (WISH) Study, a peer-led walking intervention for adolescent girls: results of a cluster randomised controlled trial.

BACKGROUND: Most adolescent girls fail to meet current physical activity guidelines. Physical activity behaviours track from childhood into adulthood and providing adolescent girls with opportunities to be physically active may have health benefits beyond childhood. The effects of walking interventions on adult cardiometabolic health are known, however less is understood about the potential of walking to promote physical activity in adolescents. Following the Walking In ScHools (WISH) feasibility study, this definitive trial aimed to evaluate the effectiveness of a novel, low-cost, school-based walking intervention at increasing physical activity levels of adolescent girls (aged 12-14 years). METHODS: Female pupils were recruited from eighteen schools across the border region of Ireland and in Northern Ireland. In intervention schools (n = 9), girls aged 15-18 years, were trained as walk leaders, and led the younger pupils in 10-15 min walks before school, at break and lunch recess. All walks took place in school grounds and pupils were encouraged to participate in as many walks as possible each week. The primary outcome measure was accelerometer determined total physical activity (counts per minutes, cpm). RESULTS: In total, 589 pupils were recruited to the study. At baseline, pupils engaged in a median (interquartile range (IQR)) 35.7 (21.2) mins moderate-vigorous physical activity (MVPA) per day and only 12% (n = 66) of participants met physical activity guidelines (60 min MVPA per day). The intervention was delivered for a mean (standard deviation (SD)) 19.9 ± 0.97 weeks. The mean post-intervention total physical activity for the intervention group was 676 cpm and 710 cpm in the control group. Post-intervention total physical activity did not statistically differ between groups when adjusted for age, body mass index z-scores and baseline physical activity (mean difference, -33.5, 95% CI = -21.2 to 88.1; p = 0.213). CONCLUSIONS: 'Scaling-up' physical activity interventions is challenging and despite a promising feasibility study, the results of this fully powered trial suggest that in this context, the WISH intervention did not increase device measured physical activity. Since the COVID-19 pandemic, school environments have changed and although pupils enjoyed the programme, attendance at walks was low, indicating that there is a need to better understand how to implement interventions within schools. TRIAL REGISTRATION: ISRCTN; ISRCTN12847782; Registered 2nd July 2019.

Clinical outcomes and frequency of persistent infection among immunosuppressed patients treated with bebtelovimab for COVID-19 infection at an ambulatory cancer center.

BACKGROUND: There are limited data on clinical outcomes associated with the use of bebtelovimab for the treatment of coronavirus disease 2019 (COVID-19) among cancer patients. We aimed to define the clinical characteristics and outcomes among patients receiving bebtelovimab as part of the COVID-19 therapeutics program at our cancer center. METHODS: This is a retrospective cohort study of immunosuppressed adult patients who received bebtelovimab at Fred Hutchinson Cancer Center between March 2022, and November 2022. We reviewed medical records to capture the date of the first positive COVID-19 test, clinical characteristics, outcomes, and follow-up COVID-19 testing for 60 days after the first positive. Persistent infection was defined as a positive test beyond day 30; these patients were reviewed beyond day 60. RESULTS: Among 93 patients who received bebtelovimab, 64 (69%) had hematologic malignancy. Sixty-nine (74%) patients received bebtelovimab within 2 days after diagnosis. Two (2%) patients were hospitalized, none required ICU care, and one patient died on day 52; although it is unknown if death was directly related to COVID-19. Ten (11%) patients had persistent COVID-19 infection; of these, four received additional COVID-19 therapy with either nirmatrelvir/ritonavir or remdesivir, and five out of six patients with sequencing data available had spike protein mutations associated with bebtelovimab resistance. CONCLUSION: A coordinated systems-based approach led to prompt initiation of bebtelovimab within two days of testing positive in most patients. We observed few hospitalizations or deaths. Persistent infection was noted in 11% of patients with four requiring additional therapies, highlighting a need for novel strategies to manage immunosuppressed patients.

In vitro cannabinoid receptor activity, metabolism, and detection in seized samples of CH-PIATA, a new indole-3-acetamide synthetic cannabinoid.

The rapidly evolving synthetic cannabinoid receptor agonist (SCRA) market poses significant challenges for forensic scientists. Since the enactment of a generic ban in China, a variety of new compounds have emerged capable of evading the legislation by carrying new structural features. One recent example of a SCRA with new linker and head moieties is CH-PIATA (CH-PIACA, CHX-PIATA, CHX-PIACA). CH-PIATA bears an additional methylene spacer in the linker moiety between the indole core and the traditional carbonyl component of the linker. This study describes detections in 2022 of this new SCRA in the United States, Belgium, and Scottish prisons. CH-PIATA was detected once in a seized powder by Belgian customs and 12 times in Scottish prisons in infused papers or resin. The metabolites of CH-PIATA were investigated via in vitro human liver microsome (HLM) incubations and eight metabolites were identified, dominated by oxidative biotransformations. A blood sample from the United States was confirmed to contain a mixture of SCRAs including CH-PIATA via presence of the parent and at least five of the metabolites identified from HLM incubations. Furthermore, this paper evaluates the intrinsic in vitro cannabinoid 1 and 2 (CB1 and CB2) receptor activation potential of CH-PIATA reference material and the powder seized by Belgian customs by means of ß-arrestin 2 recruitment assays. Both the reference and the seized powder showed a weak activity at both CB receptors with signs of antagonism found. Based on these results, the expected harm potential of this newly emerging substance remains limited.

Scrutinizing the human TEX genes in the context of human male infertility.

BACKGROUND: Infertility affects around 15% of all couples worldwide and is increasingly linked to variants in genes specifically expressed in the testis. Well-established causes of male infertility include pathogenic variants in the genes TEX11, TEX14, and TEX15, while few studies have recently reported variants in TEX13B, TEX13C, FAM9A (TEX39A), and FAM9B (TEX39B). OBJECTIVES: We aimed at screening for novel potential candidate genes among the human TEX ("testis expressed") genes as well as verifying previously described disease associations in this set of genes. MATERIALS AND METHODS: To this end, we screened the exome sequencing data of 1305 men, including 1056 crypto- and azoospermic individuals, and determined cell-specific expression by analyzing testis-specific single-cell RNA sequencing data for genes with identified variants. To investigate the overarching role in male fertility, we generated testis-specific knockdown (KD) models of all 10 orthologous TEX genes in Drosophila melanogaster. RESULTS: We detected rare potential disease-causing variants in TEX10, TEX13A, TEX13B, TEX13C, TEX13D, ZFAND3 (TEX27), TEX33, FAM9A (TEX39A), and FAM9B (TEX39B), in 28 infertile men, of which 15 men carried variants in TEX10, TEX27, and TEX33. The KD of TEX2, TEX9, TEX10, TEX13, ZFAND3 (TEX27), TEX28, TEX30, NFX1 (TEX42), TEX261, and UTP4 (TEX292) in Drosophila resulted in normal fertility. DISCUSSION: Based on our findings, the autosomal dominant predicted genes TEX10 and ZFAND3 (TEX27) and the autosomal recessive predicted gene TEX33, which all three are conceivably required for germ cell maturation, were identified as novel potential candidate genes for human non-obstructive azoospermia. We additionally identified hemizygous loss-of-function (LoF) variants in TEX13B, TEX13C, and FAM9A (TEX39A) as unlikely monogenic culprits of male infertility as LoF variants were also found in control men. CONCLUSION: Our findings concerning the X-linked genes TEX13B, TEX13C, and FAM9A (TEX39A) contradict previous reports and will decrease false-positive reports in genetic diagnostics of azoospermic men.

Analysis of health care facility-onset Clostridioides difficile infection (CDI) in a hematopoietic cell transplant (HCT) unit: A call for diagnostic stewardship in a complex patient population.

Nearly half the patients identified as having health care facility-onset Clostridioides difficile infections on a hematopoietic cell transplant unit had an alternative clinical explanation for diarrhea, including conditioning regimen toxicity or other medications. Our study supports that targeted diagnostic stewardship interventions should be explored and that additional risk-adjustments considered for facilities with oncology hematopoietic cell transplant wards in the National Healthcare Safety Network LabID Clostridioides difficile infection standardized infection ratio model.

The effect of (neo)adjuvant chemotherapy on long-term survival outcomes in patients with invasive lobular breast cancer treated with endocrine therapy: A retrospective cohort study.

BACKGROUND: Despite histological and molecular differences between invasive lobular carcinoma (ILC) and invasive carcinoma of no special type, according to national treatment guidelines no distinction is made regarding the use of (neo)adjuvant chemotherapy. Studies on the long-term outcome of chemotherapy in patients with ILC are scarce and show inconclusive results. METHODS: All patients with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative ILC with an indication for chemotherapy treated with adjuvant endocrine therapy were selected from the Erasmus Medical Center Breast Cancer database. Cox proportional hazards models were used to estimate the effect of chemotherapy on recurrence-free survival (RFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: A total of 520 patients were selected, of whom 379 were treated with chemotherapy and 141 were not. Patients in the chemotherapy group were younger (51 vs. 61 years old; p < .001), had a higher T status (T3+, 33% vs. 14%; p < .001), and more often had lymph node involvement (80% vs. 49%; p < .001) in comparison to the no-chemotherapy group. After adjusting for confounders, chemotherapy treatment was not associated with better RFS (hazard ratio [HR], 1.20; 95% confidence interval [CI], 0.63-2.31), BCSS (HR, 1.24; 95% CI, 0.60-2.58), or OS (HR, 0.97; 95% CI, 0.56-1.66). This was also reflected by adjusted Cox survival curves in the chemotherapy versus no-chemotherapy group for RFS (75% vs. 79%), BCSS (80% vs. 84%), and OS (72% vs. 71%). CONCLUSIONS: Chemotherapy is not associated with improved RFS, BCSS, or OS for patients with ER+/HER2- ILC treated with adjuvant endocrine therapy and with an indication for chemotherapy.