bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pembrolizumab in mCRPC – Combination therapies as breakthrough to success?
Authors: Plas Stefan , Pircher Andreas , Heidegger Isabel 
Published: August 2023

Purpose of review
Immune checkpoint inhibitors (ICIs) have shown promising antitumor activity in various malignant diseases. This narrative review provides an update on ongoing clinical studies investigating the only FDA-approved ICI programmed death receptor 1 (PD-1) inhibitor pembrolizumab in mono- and combination therapy in patients with metastatic castration-resistant prostate cancer (mCRPC).

Recent findings
Although most clinical trials investigating pembrolizumab as mono- or combinational therapy did not meet their primary endpoints, there exist subgroups of patients that demonstrate impressive responses rates justifying further investigation of ICI in prostate cancer. Beside combination of pembrolizumab with approved mCRPC agents, innovative approaches, like combining pembrolizumab with radioligands, deoxyribonucleic acid vaccines or innovative immunotherapeutic agents (i.e., ONC-392, AMG160, BXCL701) are ongoing exerting promising preliminary findings.

Summary
ICI monotherapy seems to be effective in a small biomarker-preselected population, however, there is evidence that especially novel ICI combination approaches can improve patient survival, which could ultimately refocus and revolutionize the treatment of mCRPC.
Analysis of predictive factors for the poor prognosis of peripheral facial paralysis
Authors: Frutos-Reoyo Emilio Javier , López-Izquierdo Raúl , Luque-Linero Paula , Cantalapiedra-Puentes Esther , Antón-Andrés María Jesús , Hernández-Gajate José Mario , Candau-Pérez Ernesto Domingo 
Published: August 2023

Abstract

PURPOSE
To evaluate the predictive factors for a poor prognosis in patients with facial paralysis evaluated in the rehabilitation department of a tertiary hospital.

METHODS
We have conducted a prospective cohort study. Patients who required elective botulinum toxin infiltration, surgical treatment, or follow-up appointments longer than 6 months due to incomplete recovery were considered to have a poor prognosis. Descriptive and analytical analyses of clinical and epidemiological variables were performed. The follow-up period was six months.

RESULTS
A total of 47 adult patients were analysed, 54.2% of whom were women. The mean age was 53.2 (SD: 15.5) years. Twenty-five percent had an unfavourable prognosis. A statistically significant association with prognosis was observed for neurophysiological results and the scores of the House-Brackmann scale and the Sunnybrook Facial Grading System.

CONCLUSION
Neurophysiological tests are especially useful when evaluating prognosis. Likewise, Sunnybrook Facial Grading System is a useful and accessible tool with prognostic value, especially within a month of initial diagnosis, when a score lower than 65 indicates a poor prognosis with high sensitivity and specificity. These tools can be especially useful to reduce the clinical and psychological impact and to provide patients with early therapeutic management.
Photo-Assisted Anthropometric Analysis of Double Eyelid Blepharoplasty in Young Chinese
Authors: Lu Menglin , Lin Wentao , Liu Jia , Wei Dayong , Shen Xiao 
Published: August 2023

Background:
Double eyelid blepharoplasty has gained popularity over decades among Asians. Quantitative assessment of the morphologic changes after double eyelid blepharoplasty remains obscure. A photo-assisted digital method was introduced to measure the outcomes of double eyelid surgery in young Chinese.

Methods:
A total of 168 Chinese patients who underwent esthetic upper blepharoplasty were recruited from October 2018 to October 2020. The participants were divided into mini-incision, full-incision, and full-incision double with epicanthoplasty (FIDE) groups. Changes in the eyeball exposure area (EEA), brow eyelid margin distance [brow eyelid distance (BED)], and palpebral crease height after surgery were analyzed using ImageJ software.

Results:
There was an overall increase in EEA in the 3 groups after upper blepharoplasty surgery. The FIDE group showed the most increase in EEA among these groups. Furthermore, BED was significantly decreased in each group after upper eyelid blepharoplasty; however, the mini-incision double group showed the least BED reduction. The palpebral crease height at 90 days was significantly lower than that at 7 days after surgery.

Conclusions:
The photo-assisted anthropometric analysis offers a simple and objective measurement for double eyelid blepharoplasty. The eyes appear larger because of the increase in EEA and decrease in BED after double eyelid blepharoplasty. Distinct results were produced by different surgical techniques. The FIDE group showed the maximum increase in EEA and a decrease in BED. These findings provide important references for preoperative planning and postoperative measurement.
Establishment of a Model for Human Hypertrophic Scar Using Tissue Engineering Method
Authors: Li Yawei , Shan Xiaofeng , Liang Jie , Cai Zhigang 
Published: August 2023

Background
Treatment of human hypertrophic scar (HS) is a challenge for plastic surgeons, whereas the clinical and experimental research has been limited due to the lack of an ideal model of human HS tissue.

Objective:
To establish a model of human HS using tissue engineering method, to improve the research for HS in the clinic and laboratory.

Methods:
Hypertrophic scar fibroblasts (HSFBs) were transferred to polylactic acid (PLA)/polyglycolic acid (PGA) scaffolds. Biocompatibility of HSFBs-PLA/PGA composites was evaluated using scanning electron microscopy. Composites of HSFBs-PLA/PGA were implanted in subcutaneous pockets in athymic mice after 4 weeks in vitro culture. A re-entry operation was performed to obtain the HS-like tissues after 12 weeks of in vivo culture. The histological stain, the expression of type I collagen, the proliferation ability, and vitality of HSFBs were compared between human HS tissue and HS-like tissue.

Results:
The structure of PLA/PGA scaffolds facilitates HSFBs adhesion and proliferation. The HSFBs-PLA/PGA composites were in vivo cultured for 12 weeks, and then HS-like tissues were harvested from nude athymic mice. There was no statistical significance in the expression of type I collagen, cell cycle, and cell proliferation between human HS tissue and HS-like tissue.

Conclusion:
The authors successfully established a model of human HS using the tissue engineering method, which could provide HS-like tissue for research. And it also could provide enough HS-like tissues to help reduce experimental variability within groups. This model can be used to investigate in prevention and treatment of HS and further explore the mechanisms of HS.
Should surgeon-performed intraoperative ultrasound be the preferred test for detecting main pancreatic duct injuries in operative trauma cases?
Authors: Ball Chad G. , Biffl Walter L. , Moore Ernest E. , Hagopian Ellen J. 
Published: August 2023

BACKGROUND
The diagnostic performance of multiple tests for detecting the presence of a main pancreatic duct injury remains poor. Given the central importance of main duct integrity for both subsequent treatment algorithms and patient outcomes, poor test reliability is problematic. The primary aim was to evaluate the comparative test performance of computed tomography (CT), magnetic resonance cholangiopancreatography (MRCP), endoscopic retrograde cholangiopancreatography (ERCP), and intraoperative ultrasound (IOUS) for detecting main pancreatic duct injuries.

METHODS
All severely injured adult patients with pancreatic trauma (2010–2021) were evaluated. Patients who received an IOUS pancreas-focused evaluation, with Grades III, IV, and V injuries (main duct injury) were compared with those with Grade I and Grade II trauma (no main duct injury). Test performances were analyzed.

RESULTS
Of 248 pancreatic injuries, 74 underwent an IOUS. The additional mix of diagnostic studies (CT, MRCP, ERCP) was variable across grade of injury. Of these 74 IOUS cases for pancreatic injuries, 48 (64.8%) were confirmed as Grades III, IV, or V main duct injuries. The patients were predominantly young (median age = 33, IQR:21–45) blunt injured (70%) males (74%) with severe injury demographics (injury severity score = 28, (IQR:19–36); 30% hemodynamic instability; 91% synchronous intra-abdominal injuries). Thirty-five percent of patients required damage-control surgery. Patient outcomes included a median 13-day hospital length of stay and 1% mortality rate. Test performance was variable across groups (CT = 58% sensitive/77% specific; MRCP = 71% sensitive/100% specific; ERCP = 100% sensitive; IOUS = 98% sensitive/100% specific).

CONCLUSION
Intraoperative ultrasound is a highly sensitive and specific test for detecting main pancreatic duct injuries. This technology is simple to learn, readily available, and should be considered in patients who require concurrent non–damage-control abdominal operations.

LEVEL OF EVIDENCE
Diagnostic Test/Criteria; Level III.
A pilot clinical trial of the Screening and Tool for Awareness and Relief of Trauma for survivors of gun violence
Authors: O'Neill Kathleen M. , Schenck Christopher , Vega Pepe , Gawel Marcie , Dodington James 
Published: August 2023

BACKGROUND
Survivors of gun violence have significant sequelae including reinjury with a firearm and mental health disorders that often go undiagnosed and untreated. The Screening and Tool for Awareness and Relief of Trauma (START) is a targeted behavioral mental health intervention developed for patients who come from communities of color with sustained and persistent trauma.

METHODS
In this pilot study, we evaluate the feasibility of completing a randomized controlled trial to test the START intervention. Using a mixed methods study design, we used both quantitative and qualitative data collection to assess the START intervention and the feasibility of completing a randomized controlled trial. The purpose of this study was to estimate important study parameters that would enable a future randomized controlled trial.

RESULTS
We were able to make conclusions about several crucial domains of a behavioral intervention trial: (1) recruitment and retention—we had a high follow-up rate, but our recruitment was low (34% of eligible participants); (2) acceptability of the intervention—the addition of audiovisual resources would make the tools more accessible; (3) feasibility of the control—more appropriate for a stepped wedge cluster randomized controlled trial design; (4) intervention fidelity—there was an 81% concordance rate between the fidelity survey results and the audio recordings; (5) approximate effect size—there was a 0.4-point decrease in the PTSD Checklist—Civilian Version in the control compared with a 10.7-point decrease in the treatment group for the first month.

CONCLUSION
While it was feasible to conduct a randomized controlled trial, our findings suggest that a stepped wedge cluster randomized controlled trial design may be the most successful trial design for the START intervention. In addition, the inclusion of a “credible messenger” to recruit participants into the study and the development of audiovisual resources for START would improve recruitment and effectiveness.

LEVEL OF EVIDENCE
Prognostic and Epidemiological; Level IV.
JMM Profile: Bacillus anthracis
Authors: Wales Andrew , Mackintosh Adrienne 
Published: August 2023

Graphical abstract
Principal routes of

Bacillus anthracis

infection and stages of anthrax pathogenesis, consistent with current understandings. Depending on the route of infection, germination of spores may happen in extracellular tissue fluid, or following phagocytosis (a). Successful infection of host cells leads to toxin-associated cell death and release of vegetative cells and toxin (b). Toxin binds and enters other host cells (c), including those of the immune system, disrupting function. In some cases this leads to systemic disease, which typically is fatal.
Adjusting for hidden biases in sexual behaviour data: a mechanistic approach
Authors: Knight Jesse , Wang Siyi , Mishra Sharmistha 
Published: August 2023

AbstractBackgroundTwo required inputs to mathematical models of sexually transmitted infections are the average duration in epidemiological risk states (e.g., selling sex) and the average rates of sexual partnership change. These variables are often only available as aggregate estimates from published cross-sectional studies, and may be subject to distributional, sampling, censoring, and measurement biases.MethodsWe explore adjustments for these biases using aggregate estimates of duration in sex work and numbers of reported sexual partners from a published 2011 survey of female sex worker in Eswatini. We develop adjustments from first principles, and construct Bayesian hierarchical models to reflect our mechanistic assumptions about the bias-generating processes.ResultsWe show that different mechanisms of bias for duration in sex work may “cancel out” by acting in opposite directions, but that failure to consider some mechanisms could over- or underestimate duration in sex work by factors approaching 2. We also show that conventional interpretations of sexual partner numbers are biased due to implicit assumptions about partnership duration, but that unbiased estimators of partnership change rate can be defined that explicitly incorporate a given partnership duration. We highlight how the unbiased estimator is most important when the survey recall period and partnership duration are similar in length.ConclusionsWhile we explore these bias adjustments using a particular dataset, and in the context of deriving inputs for mathematical modelling, we expect that our approach and insights would be applicable to other datasets and motivations for quantifying sexual behaviour data.
Strategic use of SARS-CoV-2 wastewater concentration data could enhance, but not replace, high-resolution community prevalence survey programmes
Authors: Mills Cathal , Chadeau-Hyam Marc , Elliott Paul , Donnelly Christl A. 
Published: August 2023

AbstractWastewater-based epidemiology (WBE) has been proposed as a tool for public health authorities to monitor community transmission of SARS-CoV-2 and other agents. Here, we review the utility of WBE for estimating SARS-CoV-2 prevalence using wastewater data from the Environmental Monitoring for Health Protection (EMHP) programme and prevalence data from the REal-time Assessment of Community Transmission-1 (REACT-1) study in England. Our analysis shows a temporally evolving relationship between wastewater and prevalence which limits the utility of WBE for estimating SARS-CoV-2 prevalence in high spatial resolution without a concurrent prevalence survey. We further characterise WBE for SARS-CoV-2 prevalence as i) vaccination-coverage-dependent and ii) variant-specific. Our work provides a gesopatial framework to map wastewater concentrations to public health boundaries, enabling public health authorities to interpret the relationship between wastewater and prevalence. We demonstrate that WBE can improve the cost efficiency and accuracy of community prevalence surveys which on their own may have incomplete geographic coverage or small sample sizes.
PABPN1loss-of-function in oculopharyngeal muscular dystrophy primarily impacts APA-shift in muscle transcripts
Authors: Shademan Milad , Mei Hailiang , Ariyurek Yavuz , Kloet Susan , Raz Vered 
Published: August 2023

AbstractAlternative polyadenylation (APA) at the 3’UTR of transcripts contributes to the cell transcriptome. APA is suppressed by the nuclear RNA binding protein, PABPN1. Aging-associated reduced PABPN1 levels in skeletal muscles lead to muscle wasting. Muscle weakness in oculopharyngeal muscular dystrophy (OPMD) is caused by short alanine expansion in PABPN1 exon1. The expanded PABPN1 forms nuclear aggregates, an OPMD hallmark. Whether the expanded PABPN1 affect APA and how contributes to muscle pathology is unresolved.To investigate these questions, we developed a procedure including RNA library preparation and a simple pipeline calculating ‘APA-shift’ ratio as a readout for PABPN1 function. Using the mouse OPMD model we demonstrate similar results between previously published PAS utilization and ‘APA-shift’ results. Studying APA-shift in two OPMD models and in OPMD patients we show that the expression of the expanded PABPN1 does not correlate with APA-shift. Instead, APA-shift is correlated with reduced expression levels of PABPN1 isoforms, amongst the isoform lacking exon1. Further we show that with our protocol APA-shift is enriched in muscle transcripts, moreover in OPMD patients. We suggest that muscle weakness in OPMD is caused byPABPN1loss-of-function leading to APA-shift that primarily affects in muscle transcripts.
The role of exercise in limiting progression from liver inflammation and fibrosis to cirrhosis and carcinoma: a systematic review with meta-analysis of human and animal studies
Authors: Stanhope E.N. , Drummond A.E. , Swain C.T.V. , Teoh N. , Farrell G. , Vallance J.K. , Lahart I.M. , Lynch B.M. 
Published: August 2023

AbstractBackgroundExercise may prevent the progression of liver disease and protect against liver cancer. This review with meta-analysis synthesised the evidence from both human and animal studies to better understand whether exercise has the capacity to (i) promote regression of early fibrosis; (ii) decrease and/or delay progression to cirrhosis; and (iii) progression to carcinoma.MethodsA systematic search was performed to identify studies comprising of humans and animals with liver disease that compared exercise to an inactive or less active control. Outcomes included liver disease regression and progression, and markers of liver function and damage.ResultsWe found 18 human and 29 animal studies. A single study provided direct evidence that exercise can reverse NAFLD and decrease progression to cirrhosis. Meta-analysis of human studies identified decreases in liver enzymes; ALT (SMD = -0.28, 95%CI = -0.53, -0.03), AST (SMD = -0.12, 95%CI = -0.32, 0.07), GGT (SMD = -0.23, 95%CI = -0.36, -0.10), as well as a small increase in ALP (SMD = 0.23, 95%CI = -0.13, 0.59), and liver triglycerides (SMD = -0.24, 95%CI = -0.66, 0.18). Meta-analysis of animal studies identified decreases in liver enzymes; ALT (SMD = -2.85, 95%CI = -4.55, -1.14), AST (SMD = -2.85, 95%CI = -4.55, -1.14), and liver triglycerides (SMD = -1.36, 95%CI = -2.08, -0.65), liver weight (SMD = -1.94, 95%CI = -2.78, - 1.10), and the NAFLD activity score (SMD = -1.36, 95%CI = -2.08, -0.65).ConclusionOnly one study provided direct evidence that exercise has the capacity to regress early fibrosis, as well as delay the progression to cirrhosis. Several studies, however, indicate that exercise intervention reduce markers of liver function and damage.
Qualitative protocol to support detection of the early presentation and diagnosis of mycetoma in Sudan
Authors: Ackley Caroline , Hall Victoria , Ahmed Eiman Siddig , Hounsome Natalia , Elsheikh Mohamed Nasr , Zaman Shahaduz , Bakhiet Sahar 
Published: August 2023

AbstractThe neglected tropical disease (NTD) mycetoma is a chronic and progressively destructive infectious disease endemic in Sudan. There is a growing body of scientific research on mycetoma -causes, transmission, treatment, and impact from a clinical and biomedical perspective. However, there is further need for in-depth medical anthropology research on the disease to successfully translate biomedical advances into elimination and control programmes. Given this background the NIHR Global Health Research Unit on NTDs at Brighton and Sussex Medical School is leading multidisciplinary research on skin NTDs, including mycetoma, with a medical anthropology research component exploring how community engagement can lead to earlier presentation of mycetoma in Sudan. This protocol paper sets out the research aims and approaches to generate new knowledge on mycetoma in Sudan once the political situation becomes stable and it is safe to carry out global health research once again. We continue to develop appropriate community engagement intervention strategies, while activities like training and capacity strengthening get underway remotely.
Additively manufactured multiplexed electrochemical device (AMMED) for portable sample-to-answer detection
Authors: Jahromi Arash Khorrami , Moakhar Roozbeh Siavash , Yedire Sripadh Guptha , Shieh Hamed , Rosenflanz Katia , Bricks Amber , de Vries Justin , Lu Yao , Shafique Houda , Strauss Julia , Mahshid Sara 
Published: August 2023

AbstractPortable sample-to-answer devices with applications in point-of-care settings have emerged to obviate the necessity of centralized laboratories for biomarker analysis. In this work, a smartphone-operated and additively manufactured multiplexed electrochemical device (AMMED) is presented for the portable detection of biomarkers in blood and saliva. AMMED is comprised of a customized portable potentiostat with a multiplexing feature, a 3D-printed sample collection cartridge to handle three samples of saliva and blood at the same time, a smartphone application to remotely control the potentiostat, and a 3D-printed-based multiplexed microfluidic electrochemical biosensor (test chip). Here, by employing additive manufacturing techniques, a simple, cleanroom-free, and scalable approach was proposed for the fabrication of the test chip. Moreover, these techniques can bring about easy integration of AMMED components. Additionally, the test chip can be compatible with different affinity-based bioassays which can be implemented in a multiplexed manner for detection. The AMMED components were successfully characterized in terms of electrochemical and fluidic performance. Particularly, to demonstrate the biosensing capabilities of the device, the spike protein of the SARS-CoV-2 omicron variant and a well-established aptameric assay were selected as the representative biomarker and the bioassay, respectively. The proposed device accurately and selectively detected the target of interest in a rapid (5 min) and multiplex manner with a dynamic detection range of 1–10,000 pg. ml-1in different media; and the clinical feasibility was assessed by several saliva patient samples. AMMED offers a versatile sample-to-answer platform that can be used for the detection of various biomarkers present in biofluids.
ClairS: a deep-learning method for long-read somatic small variant calling
Authors: Zheng Zhenxian , Su Junhao , Chen Lei , Lee Yan-Lam , Lam Tak-Wah , Luo Ruibang 
Published: August 2023

AbstractIdentifying somatic variants in tumor samples is a crucial task, which is often performed using statistical methods and heuristic filters applied to short-read data. However, with the increasing demand for long-read somatic variant calling, existing methods have fallen short. To address this gap, we present ClairS, the first deep-learning-based, long-read somatic small variant caller. ClairS was trained on massive synthetic somatic variants with diverse coverages and variant allele frequencies (VAF), enabling it to accurately detect a wide range of somatic variants from paired tumor and normal samples. We evaluated ClairS using the latest Nanopore Q20+ HCC1395-HCC1395BL dataset. With 50-fold/25-fold tumor/normal, ClairS achieved a 93.01%/86.86% precision/recall rate for Single Nucleotide Variation (SNVs), and 66.54%/66.89% for somatic insertions and deletions (Indels). Applying ClairS to short-read datasets from multiple sources showed comparable or better performance than Strelka2 and Mutect2. Our findings suggest that improved read phasing enabled by long-read sequencing is key to accurate long-read SNV calling, especially for variants with low VAF. Through experiments across various coverage, purity, and contamination settings, we demonstrated that ClairS is a reliable somatic variant caller. ClairS is open-source athttps://github.com/HKU-BAL/ClairS.