Examining Linguistic Differences in Electronic Health Records for Diverse Patients With Diabetes: Natural Language Processing Analysis.

Background: Individuals from minoritized racial and ethnic backgrounds experience pernicious and pervasive health disparities that have emerged, in part, from clinician bias. Objective: We used a natural language processing approach to examine whether linguistic markers in electronic health record (EHR) notes differ based on the race and ethnicity of the patient. To validate this methodological approach, we also assessed the extent to which clinicians perceive linguistic markers to be indicative of bias. Methods: In this cross-sectional study, we extracted EHR notes for patients who were aged 18 years or older; had more than 5 years of diabetes diagnosis codes; and received care between 2006 and 2014 from family physicians, general internists, or endocrinologists practicing in an urban, academic network of clinics. The race and ethnicity of patients were defined as White non-Hispanic, Black non-Hispanic, or Hispanic or Latino. We hypothesized that Sentiment Analysis and Social Cognition Engine (SEANCE) components (ie, negative adjectives, positive adjectives, joy words, fear and disgust words, politics words, respect words, trust verbs, and well-being words) and mean word count would be indicators of bias if racial differences emerged. We performed linear mixed effects analyses to examine the relationship between the outcomes of interest (the SEANCE components and word count) and patient race and ethnicity, controlling for patient age. To validate this approach, we asked clinicians to indicate the extent to which they thought variation in the use of SEANCE language domains for different racial and ethnic groups was reflective of bias in EHR notes. Results: We examined EHR notes (n=12,905) of Black non-Hispanic, White non-Hispanic, and Hispanic or Latino patients (n=1562), who were seen by 281 physicians. A total of 27 clinicians participated in the validation study. In terms of bias, participants rated negative adjectives as 8.63 (SD 2.06), fear and disgust words as 8.11 (SD 2.15), and positive adjectives as 7.93 (SD 2.46) on a scale of 1 to 10, with 10 being extremely indicative of bias. Notes for Black non-Hispanic patients contained significantly more negative adjectives (coefficient 0.07, SE 0.02) and significantly more fear and disgust words (coefficient 0.007, SE 0.002) than those for White non-Hispanic patients. The notes for Hispanic or Latino patients included significantly fewer positive adjectives (coefficient -0.02, SE 0.007), trust verbs (coefficient -0.009, SE 0.004), and joy words (coefficient -0.03, SE 0.01) than those for White non-Hispanic patients. Conclusions: This approach may enable physicians and researchers to identify and mitigate bias in medical interactions, with the goal of reducing health disparities stemming from bias.

Spontaneous middle lobe torsion: An institutional case series.

Objective: Lobar torsion is a rare occurrence in which a portion of the lung is twisted on its bronchovascular pedicle. The vast majority are observed in the acute postoperative period often following right upper lobectomy. Spontaneous middle lobe torsion independent of pulmonary resection is exceptionally rarer; fewer than 15 cases have been recorded. We present an institutional case series of 2 patients postorthotopic liver transplantation who developed spontaneous middle lobe torsion due to large pleural effusions. Methods: We provide the medical course as well as intraoperative techniques for our 2 patients along with a review of the literature. Results: Both patients in this case series underwent orthotopic liver transplant complicated postoperatively by a large pulmonary effusion. Patient one developed an abdominal hematoma requiring evacuation and repair, after which he developed progressive shortness of breath. Bronchoscopy revealed a right middle lobe obstruction; upon thoracotomy, 180-degree torsion with widespread necrosis was evident and the middle lobe was removed. He is doing well to date. Patient 2 experienced postoperative pleural effusion and mucus plugging; computed tomography revealed abrupt middle lobe arterial occlusion prompting urgent operative intervention. Again, the middle lobe was grossly ischemic and dissection revealed a 360-degree torsion around the pedicle. It was resected. He is doing well to date. Conclusions: As the result of its rarity, radiographic and clinical diagnosis of spontaneous pulmonary lobar torsion is challenging; a high index of suspicion for spontaneous middle lobe torsion must be maintained to avoid delays in diagnosis. Prompt surgical intervention is essential to improve patient outcomes.

Organization of the human intestine at single-cell resolution.

The intestine is a complex organ that promotes digestion, extracts nutrients, participates in immune surveillance, maintains critical symbiotic relationships with microbiota and affects overall health1. The intesting has a length of over nine metres, along which there are differences in structure and function2. The localization of individual cell types, cell type development trajectories and detailed cell transcriptional programs probably drive these differences in function. Here, to better understand these differences, we evaluated the organization of single cells using multiplexed imaging and single-nucleus RNA and open chromatin assays across eight different intestinal sites from nine donors. Through systematic analyses, we find cell compositions that differ substantially across regions of the intestine and demonstrate the complexity of epithelial subtypes, and find that the same cell types are organized into distinct neighbourhoods and communities, highlighting distinct immunological niches that are present in the intestine. We also map gene regulatory differences in these cells that are suggestive of a regulatory differentiation cascade, and associate intestinal disease heritability with specific cell types. These results describe the complexity of the cell composition, regulation and organization for this organ, and serve as an important reference map for understanding human biology and disease.

Racial/Ethnic Minority Identifying Family Physicians Are More Likely to Work in Solo Practices.

While the overall proportion of family physicians who work in solo practices has been steadily declining, Black, Hispanic/Latino, and Asian family physicians are more likely to work in these settings. Given their association with high levels of continuity and improved health outcomes, and given patient preference for racial concordance with their physicians, policy makers and payors should consider how to support family physicians in solo practice in the interest of promoting access to and quality of care for ethnic/racial minorities.

Declining Medicare reimbursement in abdominal transplantation from 2000 to 2021.

BACKGROUND: The Centers for Medicare and Medicaid Services is a major payer for abdominal transplant services. Reimbursement reductions could have a major impact on the transplant surgical workforce and hospitals. Yet government reimbursement trends in abdominal transplantation have not been fully characterized. METHODS: We performed an economic analysis to characterize changes in inflation-adjusted trends in Medicare surgical reimbursement for abdominal transplant procedures. Using the Medicare Fee Schedule Look-Up Tool, we performed a procedure code-based surgical reimbursement rate analysis. Reimbursement rates were adjusted for inflation to calculate overall changes in reimbursement, overall year-over-year, 5-year year-over-year, and compound annual growth rate from 2000 to 2021. RESULTS: We observed declines in adjusted reimbursement of common abdominal transplant procedures, including liver (-32.4%), kidney with and without nephrectomy (-24.2% and -24.1%, respectively), and pancreas transplant (-15.2%) (all, P < .05). Overall, the yearly average change for liver, kidney with and without nephrectomy, and pancreas transplant were -1.54%, -1.15%, -1.15%, and -0.72%. Five-year annual change averaged -2.69%, -2.35%, -2.64%, and -2.43%, respectively. The overall average compound annual growth rate was -1.27%. CONCLUSION: This analysis depicts a worrisome reimbursement pattern for abdominal transplant procedures. Transplant surgeons, centers, and professional organizations should note these trends to advocate sustainable reimbursement policy and to preserve continued access to transplant services.

Outcomes of a Large Series of Laparoscopic Ventral Hernia Repairs after Liver Transplantation.

BACKGROUND: The hernia defects that develop in liver transplant recipients tend to be complex. Unfortunately, there is a paucity of data to guide post-transplant hernia management. Our goal was to evaluate the outcomes following laparoscopic ventral hernia repair (LVHR) in liver transplant recipients. METHODS: A retrospective review of a prospectively kept database of liver transplant patients at a single tertiary healthcare facility was completed. All patients between 2007 and 2020 who underwent LVHR for a hernia at their transplant incision site were included. The primary outcome studied was hernia recurrence. Secondary outcomes included time-to-hernia repair, complications, and length of stay (LOS). RESULTS: There were 89 patients who met inclusion criteria. 82% were male, mean age was 60 years, and mean body mass index was 30.2 kg/m2. 94.4% were on tacrolimus and 36% on mycophenolate mofetil. Median time-to-hernia repair was 16 months with a mean mesh size of 743 cm2 and length of stay of 3.7 days. None required conversion to an open operation. Postoperative complications included ileus (20.2%), acute kidney injury (11.2%), pneumonia (6.7%), and bleeding requiring re-operation (1.1%). Hernia-related complications included chronic suture site pain (1.1%), seroma requiring intervention (3.3%), surgical site infection (3.3%), nonoperative mesh infection (1.1%), and mesh infection requiring explantation (1.1%). Median follow-up was 23 months. Hernia recurrence occurred in 4.5% and no predictive variables for recurrence were identified. CONCLUSIONS: Although the hernia defects that develop in liver transplant recipients are complex and their comorbidities significant, LVHR can safely and effectively repair these defects with low rates of recurrence and complications.

An Assessment of How Clinicians and Staff Members Use a Diabetes Artificial Intelligence Prediction Tool: Mixed Methods Study.

BACKGROUND: Nearly one-third of patients with diabetes are poorly controlled (hemoglobin A1c≥9%). Identifying at-risk individuals and providing them with effective treatment is an important strategy for preventing poor control. OBJECTIVE: This study aims to assess how clinicians and staff members would use a clinical decision support tool based on artificial intelligence (AI) and identify factors that affect adoption. METHODS: This was a mixed methods study that combined semistructured interviews and surveys to assess the perceived usefulness and ease of use, intent to use, and factors affecting tool adoption. We recruited clinicians and staff members from practices that manage diabetes. During the interviews, participants reviewed a sample electronic health record alert and were informed that the tool uses AI to identify those at high risk for poor control. Participants discussed how they would use the tool, whether it would contribute to care, and the factors affecting its implementation. In a survey, participants reported their demographics; rank-ordered factors influencing the adoption of the tool; and reported their perception of the tool's usefulness as well as their intent to use, ease of use, and organizational support for use. Qualitative data were analyzed using a thematic content analysis approach. We used descriptive statistics to report demographics and analyze the findings of the survey. RESULTS: In total, 22 individuals participated in the study. Two-thirds (14/22, 63%) of respondents were physicians. Overall, 36% (8/22) of respondents worked in academic health centers, whereas 27% (6/22) of respondents worked in federally qualified health centers. The interviews identified several themes: this tool has the potential to be useful because it provides information that is not currently available and can make care more efficient and effective; clinicians and staff members were concerned about how the tool affects patient-oriented outcomes and clinical workflows; adoption of the tool is dependent on its validation, transparency, actionability, and design and could be increased with changes to the interface and usability; and implementation would require buy-in and need to be tailored to the demands and resources of clinics and communities. Survey findings supported these themes, as 77% (17/22) of participants somewhat, moderately, or strongly agreed that they would use the tool, whereas these figures were 82% (18/22) for usefulness, 82% (18/22) for ease of use, and 68% (15/22) for clinic support. The 2 highest ranked factors affecting adoption were whether the tool improves health and the accuracy of the tool. CONCLUSIONS: Most participants found the tool to be easy to use and useful, although they had concerns about alert fatigue, bias, and transparency. These data will be used to enhance the design of an AI tool.

A comprehensive thermodynamic model for RNA binding by the Saccharomyces cerevisiae Pumilio protein PUF4.

Genomic methods have been valuable for identifying RNA-binding proteins (RBPs) and the genes, pathways, and processes they regulate. Nevertheless, standard motif descriptions cannot be used to predict all RNA targets or test quantitative models for cellular interactions and regulation. We present a complete thermodynamic model for RNA binding to the S. cerevisiae Pumilio protein PUF4 derived from direct binding data for 6180 RNAs measured using the RNA on a massively parallel array (RNA-MaP) platform. The PUF4 model is highly similar to that of the related RBPs, human PUM2 and PUM1, with one marked exception: a single favorable site of base flipping for PUF4, such that PUF4 preferentially binds to a non-contiguous series of residues. These results are foundational for developing and testing cellular models of RNA-RBP interactions and function, for engineering RBPs, for understanding the biophysical nature of RBP binding and the evolutionary landscape of RNAs and RBPs.

Single-cell analyses define a continuum of cell state and composition changes in the malignant transformation of polyps to colorectal cancer.

To chart cell composition and cell state changes that occur during the transformation of healthy colon to precancerous adenomas to colorectal cancer (CRC), we generated single-cell chromatin accessibility profiles and single-cell transcriptomes from 1,000 to 10,000 cells per sample for 48 polyps, 27 normal tissues and 6 CRCs collected from patients with or without germline APC mutations. A large fraction of polyp and CRC cells exhibit a stem-like phenotype, and we define a continuum of epigenetic and transcriptional changes occurring in these stem-like cells as they progress from homeostasis to CRC. Advanced polyps contain increasing numbers of stem-like cells, regulatory T cells and a subtype of pre-cancer-associated fibroblasts. In the cancerous state, we observe T cell exhaustion, RUNX1-regulated cancer-associated fibroblasts and increasing accessibility associated with HNF4A motifs in epithelia. DNA methylation changes in sporadic CRC are strongly anti-correlated with accessibility changes along this continuum, further identifying regulatory markers for molecular staging of polyps.

High-throughput biochemical profiling reveals functional adaptation of a bacterial Argonaute.

Argonautes are nucleic acid-guided proteins that perform numerous cellular functions across all domains of life. Little is known about how distinct evolutionary pressures have shaped each Argonaute's biophysical properties. We applied high-throughput biochemistry to characterize how Thermus thermophilus Argonaute (TtAgo), a DNA-guided DNA endonuclease, finds, binds, and cleaves its targets. We found that TtAgo uses biophysical adaptations similar to those of eukaryotic Argonautes for rapid association but requires more extensive complementarity to achieve high-affinity target binding. Using these data, we constructed models for TtAgo association rates and equilibrium binding affinities that estimate the nucleic acid- and protein-mediated components of the target interaction energies. Finally, we showed that TtAgo cleavage rates vary widely based on the DNA guide, suggesting that only a subset of guides cleaves targets on physiologically relevant timescales.

Primary Care: The Actual Intelligence Required for Artificial Intelligence to Advance Health Care and Improve Health.

With conversational agents triaging symptoms, cameras aiding diagnoses, and remote sensors monitoring vital signs, the use of artificial intelligence (AI) outside of hospitals has the potential to improve health, according to a recently released report from the National Academy of Medicine. Despite this promise, the success of AI is not guaranteed, and stakeholders need to be involved with its development to ensure that the resulting tools can be easily used by clinicians, protect patient privacy, and enhance the value of the care delivered. A crucial stakeholder group missing from the conversation is primary care. As the nation's largest delivery platform, primary care will have a powerful impact on whether AI is adopted and subsequently exacerbates health disparities. To leverage these benefits, primary care needs to serve as a medical home for AI, broaden its teams and training, and build on government initiatives and funding.

Solid Organ Transplantation From SARS-CoV-2-infected Donors to Uninfected Recipients: A Single-center Experience.

BACKGROUND: The risk of donor-derived severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in solid organ (heart, lung, liver, kidney, pancreas, and intestine) transplant recipients is poorly understood. Since hematogenous transmission of SARS-CoV-2 has not been documented to date, nonlung solid organs might be suitable for transplantation since they likely portend a low risk of viral transmission. METHODS: Abdominal solid organs from SARS-CoV-2-infected donors were transplanted into uninfected recipients. RESULTS: Between April 18, 2021, and October 30, 2021, we performed transplants of 2 livers, 1 simultaneous liver and kidney, 1 kidney, and 1 simultaneous kidney and pancreas from SARS-CoV-2-infected donors into 5 uninfected recipients. None of the recipients developed SARS-CoV-2 infection or coronavirus disease 2019, and when tested, allograft biopsies showed no evidence of SARS-CoV-2 RNA. CONCLUSIONS: Transplanting nonlung organs from SARS-CoV-2-infected donors into uninfected recipients demonstrated no evidence of virus transmission.

Utilization of Veno-Arterial Extracorporeal Life Support for Acute Respiratory Distress Syndrome After Liver Transplant.

In this report, we present a case of successful long-term salvage of a patient with transfusion-related acute lung injury associated with acute respiratory distress syndrome immediately after a liver transplant. The patient was a 29-year-old man with end-stage liver disease due to sclerosing cholangitis who underwent liver transplant. After organ reperfusion, there was evidence of liver congestion, acidosis, coagulopathy, and acute kidney injury. He received 61 units of blood products. Continuous renal replacement therapy was initiated intraoperatively. On arrival to the intensive care unit, the patient was on high-dose pressors, and the patient developed respiratory failure and was immediately placed on veno-arterial extracorporeal membrane oxygenation via open femoral exposure. The patient presented with severe coagulopathy and early allograft dysfunction; therefore, no systemic heparin was administered and no thrombotic events occurred. He required extracorporeal membrane oxygenation support until posttransplant day 4, when resolution of the respiratory and cardiac dysfunction was noted. At 2 years after liver transplant, the patient has normal liver function, normal cognitive function, and stage V chronic kidney disease. We conclude that extracorporeal membrane oxygenation is a valuable therapeutic approach in patients with cardiorespiratory failure after liver transplant.

Alloantibodies after simultaneous liver-kidney transplant: A story of primary nonfunction, retransplantation, and antibody-mediated rejection.

Simultaneous liver-kidney transplant (SLKT) in the presence of antihuman leukocyte antigen (HLA) donor-specific antibodies (DSA) is a well-accepted practice. Herein, we describe the evolution of alloantibodies in a patient who received an SLKT. The pre-SLKT serum sample showed multiple strong DSA. As expected, all DSA cleared in a sample collected 4 days after the SLKT. Because of the primary nonfunction of the liver in the SLKT, the patient had a second liver transplant 4 days later. An abrupt increase in DSA levels against the kidney was detected 10 days after the second liver transplant. These DSA were refractory to treatment, and the transplanted kidney was lost due to antibody-mediated rejection (AMR). A detailed study of the HLA epitopes recognized by DSA and, after normalization with third-party alloantibodies to address the effect of multiple transfusions and liver allograft neutralization, showed that the elimination of these antibodies depended on the HLA antigens expressed by the transplanted liver cells. The return of DSA after removal of the first transplanted liver was associated with AMR in the transplanted kidney.

An Efficient Method for the Euthanasia of Cane Toads (Rhinella marina) under Northern Australian Field Conditions.

The euthanasia of cane toads under field conditions presents a number of logistical and animal welfare challenges. One recommended method of control involves the use of carbon dioxide in plastic bags. This paper describes the minimum amount of time (4 h) required to efficiently euthanase toads with a carbon dioxide concentration of 4.96% under field conditions experienced in northern Australia. Discussion is also provided on the issues of safe disposal of biological and plastic waste associated with the application of this method.

Quantification of Cas9 binding and cleavage across diverse guide sequences maps landscapes of target engagement.

The RNA-guided nuclease Cas9 has unlocked powerful methods for perturbing both the genome through targeted DNA cleavage and the regulome through targeted DNA binding, but limited biochemical data have hampered efforts to quantitatively model sequence perturbation of target binding and cleavage across diverse guide sequences. We present scalable, sequencing-based platforms for high-throughput filter binding and cleavage and then perform 62,444 quantitative binding and cleavage assays on 35,047 on- and off-target DNA sequences across 90 Cas9 ribonucleoproteins (RNPs) loaded with distinct guide RNAs. We observe that binding and cleavage efficacy, as well as specificity, vary substantially across RNPs; canonically studied guides often have atypically high specificity; sequence context surrounding the target modulates Cas9 on-rate; and Cas9 RNPs may sequester targets in nonproductive states that contribute to "proofreading" capability. Lastly, we distill our findings into an interpretable biophysical model that predicts changes in binding and cleavage for diverse target sequence perturbations.

Increased access to liver transplantation for patients with acute on chronic liver failure after implementation of Share 35 Rule: An analysis from the UNOS database.

INTRODUCTION AND OBJECTIVES: Acute on chronic liver failure (ACLF), leads to high mortality. These patients are at risk of being delisted for liver transplantation (LT). Emerging data shows 1y post-transplant survival of 80-92%. The Share 35 (S35) policy was implemented to prioritize patients with MELD ≥35 on the LT waitlist. Our aim was to compare the LT outcomes of ACLF patients as a result of S35. MATERIALS AND METHODS: Data from the UNOS scientific registry were used to classify ACLF patients using the NACSELD criteria. For the analyses, data were divided into two eras; 2 years before S35 (Era 1) and 2 years after S35 (Era 2). Waitlist status was classified into categories: Transplanted, Death or Too Sick to Transplant and Still Waiting/Other. LT cumulative incidence between the populations in the eras was calculated using Fine and Gray's method. A proportional hazards model was used to investigate the era effect on cumulative incidence of LT. RESULTS: 46,861 patients were reviewed, of which 817 had ACLF. 366 patients (mean MELD: 37.1) were identified in Era 1 and 451 patients (mean MELD: 37.3) in Era 2. We found that ACLF patients were more likely to receive a liver transplant in Era 2 (p=0.0074). In both eras, transplanted patients had a significantly higher survival than those who were not transplanted (p<0.0001). CONCLUSIONS: Our study shows that S35 improved LT rate for ACLF suggesting that there should be broader recognition of ACLF and early transplantation should be pursued.

Robot Assisted Renal Allograft Nephrectomy: Initial Case Series and Description of Technique.

OBJECTIVE: To evaluate the outcomes and perioperative complication rates following robot- assisted transplant nephrectomy ((RATN). METHODS: All patients who underwent RATN at our institution were included. No exclusion criteria were applied. Clinical records were retrospectively reviewed and reported. This included preoperative, intraoperative, and postoperative outcomes. Complications were reported utilizing the Clavien-Dindo classification system. Descriptive statistics were reported using frequencies and percentages for categorical variables, means and standard deviation for continuous variables. RESULTS: Between July 2014 and April 2018, 15 patients underwent RATN. Most patients had the transplant in the right iliac fossa (13/15). Ten patients underwent a concomitant procedure. The total operative time for the entire cohort was 336 (±102) minutes (including cases who had concomitant procedures) and 259 (±46 minutes) when cases with concomitant procedures were excluded. Mean estimated blood loss was 383 (±444) mL. Postoperatively, 3 patients required blood transfusion. Average hospital stay was 4 (±2.7) days. Most patients had finding consistent with graft rejection on final pathology. There were 5 complications; 3 of which were minor (grade 2 = 2 and grade 3 = 1); one patient had a wound infection requiring dressing (3A) and one patient died due to pulmonary embolism following discharge. Limitations include small series and retrospective nature of the study. CONCLUSION: This case series demonstrate that RATN is technically feasible. With continued experience and larger case series, the robotic approach may provide a minimally invasive alternative to open allograft nephrectomy.

How do aggression source, employee characteristics and organisational response impact the relationship between workplace aggression and work and health outcomes in healthcare employees? A cross-sectional analysis of the National Health Service staff survey in England.

OBJECTIVES: To examine the prevalence of aggression in healthcare and its association with employees' turnover intentions, health and engagement, as well as how these effects differ based on aggression source (patients vs colleagues), employee characteristics (race, gender and occupation) and organisational response to the aggression. DESIGN: Multilevel moderated regression analysis of 2010 National Health Service (NHS) survey. SETTING: 147 acute NHS trusts in England. PARTICIPANTS: 36 850 participants across three occupational groups (14% medical/dental, 61% nursing/midwifery, 25% allied health professionals or scientific and technical staff). MAIN OUTCOME MEASURES: Employee turnover intentions, health and work engagement. RESULTS: Both forms of aggression (from patients and colleagues) have significant and substantial effects on turnover intentions, health and work engagement; however, for all three outcome variables, the effect of aggression from colleagues is more than twice the size of the effect of aggression from patients. Organisational response was found to buffer the negative effects of aggression from patients for turnover intentions and the negative effects of aggression from patients and colleagues for employee health. The results also demonstrated that nurses/midwives, women and Black employees are more likely to experience aggression; however, no clear patterns emerged on how aggression differentially impacts employees of different races, genders and occupations with respect to the outcome variables. CONCLUSIONS: Although aggression from patients and colleagues both have negative effects on healthcare employees' turnover intentions, health and work engagement, these negative effects are worse when it is aggression from colleagues. Having an effective organisational response can help ameliorate the negative effects of aggression on employees' health; however, it may not always buffer negative effects on turnover intentions and work engagement. Future research should examine other approaches, as well as how organisational responses and resources may need to differ based on aggression source.

High fat diet causes distinct aberrations in the testicular proteome.

Diet has important effects on normal physiology and the potential deleterious effects of high fat diets and obesity on male reproductive health are being increasingly described. We conducted a histological review of the effects of chronic high fat (HF) diet (using a mouse model fed a 45% fat diet for 21 weeks) with a discovery proteomic study to assess for changes in the abundance of proteins in the testis. Mice on a HF diet became obese and developed glucose intolerance. Using mass spectrometry, we identify 102 proteins affected in the testis of obese mice. These included structural proteins important for the blood testis barrier (filamin A, FLNA), proteins involved in oxidative stress responses (spermatogenesis associated 20, SPATA-20) and lipid homoeostasis (sterol regulatory element-binding protein 2, SREBP2 and apolipoprotein A1, APOA1). In addition, an important regulator protein paraspeckle component 1, PSPC-1, which interacts with the androgen receptor was significantly downregulated. Proteomic data was validated using both Western blotting and immunostaining which confirmed and localised protein expression in both mouse and human testis using biopsy specimens. This study focused mainly on the abnormalities that occurred at the protein level and as a result, we have identified several candidate proteins and conducted pathway analysis around the effects of HF diet on the testis providing novel insights not previously described. Some of the identified targets could be targeted therapeutically and future work is directed in this area.