bluuebunny/crossref_metadata_2025_split huggingface dataset:
24-Hour Ex Vivo Hypothermic Acellular Perfusion of Porcine Forelimb: A 7-Day Follow-up Study
Authors: Brouwers Kaj , Kruit Anne Sophie , van Midden Dominique , Zegers Her J. H. , Doorduin Jonne , Koers Erik , Hummelink Stefan , Ulrich Dietmar J. O. 
Published: April 2024

Background:
One of the limiting factors for vascularized composite allograft storage is the short viable ischemic time (4 to 6 hours). Hypothermic machine perfusion enables near-physiologic preservation, avoiding the deleterious effects of hypoxia and static cooling. This study aims to compare muscle injury after 24-hour acellular perfusion with static cold storage (SCS) in a porcine limb replantation model, examining outcomes for up to 7 days after reperfusion.

Methods:
Sixteen procured porcine forelimbs were perfused under hypothermic conditions for 24 hours with histidine-tryptophan-ketoglutarate (n = 8) or preserved on ice for 4 hours (SCS; n = 8) before heterotopic replantation. Muscle injury was assessed using biochemical markers, and muscle biopsies were analyzed using the Histologic Injury Severity Score.

Results:
During preservation, limb weight decreased by 2% in the SCS group and increased by 44% in the perfusion group (P < 0.001). Twelve limbs (histidine-tryptophan-ketoglutarate, n = 6; SCS, n = 6) survived for 7 days. Three days after replantation, increased creatinine kinase levels were observed in the perfusion group (33,781 versus 2163 mmol/L; P < 0.001). The mean end point Histologic Injury Severity Score was 3.8 (SD 0.7) in the perfusion group and 1.8 (SD 0.7) in the SCS group (P = 0.008), mostly due to increased edema (P = 0.004).

Conclusion:
A total of 24 hours of hypothermic machine perfusion and 4 hours of SCS of the vascularized composite allograft demonstrated minimal degenerated muscle tissue 7 days after replantation.

Clinical Relevance Statement:
This project will widely advance the field of reconstructive research and provide strong preclinical data to allow human clinical trials with great potential to change the standard of care in reconstructive transplantation.
Estimating the Effect of COVID-19 Pandemic Restrictions on Self-reported Antiretroviral Therapy Use and Late Refill Visits Among People Living With HIV in Rural South Africa
Authors: Tseng Ashley S. , Mugwanya Kenneth K. , Szpiro Adam A. , van Heerden Alastair , Ntinga Xolani , Schaafsma Torin T. , Barnabas Ruanne V. 
Published: April 2024

Background:
People living with HIV require reliable access to and adequate supply of antiretroviral therapy (ART) for viral suppression. The Deliver Health Study, a randomized trial conducted during the COVID-19 pandemic, found that home-delivered ART significantly increased viral suppression compared with clinic-based care. The effect of changing COVID-19 alert levels on self-reported ART use has not been quantified.

Setting:
KwaZulu-Natal, South Africa.

Methods:
Adults living with HIV were followed in the Deliver Health Study during October 2019–December 2020. We used difference-in-differences (DiD) to estimate the effect of changing COVID-19 alert levels during 3 distinct periods on self-reported missed ART doses (missed 0 vs. ≥1 doses in past week) for participants receiving home-delivered vs. clinic-based refills. We additionally estimated the effect of changing COVID-19 alert levels on late clinic ART refill visits (late vs. on-time). We used relative risk regression for both binary outcomes.

Results:
Of 155 participants, 46% were women and the median age was 36 years. The mean number of missed weekly doses was 0.11, 0, and 0.12 in the home-delivery group and 0.09, 0.08, and 0.18 in the clinic group during periods 1, 2, and 3, respectively. There were no differences in relative risk of self-reported daily ART use between refill groups when comparing across periods [DiDperiod 2 vs. 1 = 1.05; 95% confidence interval: 0.97, 1.13 and DiDperiod 3 vs. 2 = 0.99; 95% confidence interval (CI): 0.91, 1.08]. In the clinic group, the risk of late refill visits was significantly higher during COVID-19 restrictions (vs. before alert level 5 implementation) and even after the COVID-19 alert level was downgraded to level 1 (RRperiod 2 vs. 1 = 1.83, 95% CI: 1.34, 2.51 and RRperiod 3 vs. 2 = 1.71; 95% CI: 1.43, 2.04).

Conclusion:
The COVID-19 pandemic did not differentially impact self-reported ART adherence by the method of ART refills, but the risk of late clinic refill visits was significantly higher during COVID-19 restrictions and sustained after restrictions were loosened.
18F-FDG PET/CT of Intracholecystic Papillary Neoplasm in Cystic Neck and Duct
Authors: Xu Jun-Yu , Shuai Yong-Kang , Xie Yan-Ping , Cao Su-E , Zou Qiong 
Published: April 2024

Abstract
We report 18F-FDG PET/CT appearances of intracholecystic papillary neoplasm (ICPN) in the gallbladder neck and duct of a 74-year-old woman with a history of hepatitis B cirrhosis. The lesion presented with a large and sessile soft mass in the neck and duct of gallbladder with obvious glucose metabolism on PET/CT images, which was confirmed pathologically as ICPN (gastric foveolar type) with high-grade intraepithelial neoplasia. ICPN localized in the gallbladder neck and duct is extremely rare, and is easily misdiagnosed as gallbladder carcinoma. Our report aids in the application of PET/CT in the differential diagnosis of ICPN and guiding early surgery.
Enhancing Cerebral Amyloid Angiopathy–Related Inflammation Diagnosis With PET Using Pittsburgh Compound B
Authors: Adaniya Shinobu , Matsuda Hiroshi , Tomori Masaki , Kaneko Chikako , Tomura Noriaki 
Published: April 2024

Abstract
Cerebral amyloid angiopathy–related inflammation is a rare encephalopathy characterized by inflammation against amyloid protein accumulated in cerebral small vessels. A 50-year-old man was presented with a subacute consciousness disorder. Brain MRI revealed high intensity lesions in the white matter of the right parietal and occipital lobes on fluid-attenuated inversion recovery sequences and cerebral microbleeds in the right parietal and occipital lobes on T2*-weighted images. Pittsburgh compound B-PET demonstrated accumulation in the right temporoparietal lobe, confirming a potential diagnosis of probable cerebral amyloid angiopathy–related inflammation without brain biopsy. Steroid pulse therapy was initiated, with good results.
Utilization and Cost of Gender-affirming Surgery in the United States from 2012-2019
Authors: Chu Jacky , Nagpal Meera , Dobberfuhl Amy D. 
Published: April 2024

Objective:
To characterize the trends in and characteristics associated with the utilization and cost of gender-affirming surgery (GAS) in the United States from 2012-2019.

Summary Background Data:
GAS is one option among gender-diverse (GD) people to transition from their biologic anatomy to the anatomy congruent with their gender. Little is known about its utilization and cost trends and whether patient and hospital characteristics are associated with differences in utilization and cost.

Methods:
This serial cross-sectional study collected retrospective data from the Healthcare Cost and Utilization Project (HCUP) National Inpatient Sample (NIS), a representative pool of inpatient visits in the United States. Records from 2012-2019 that indicated ages 18 or older, GD diagnoses, and GAS procedures were identified using the International Classification of Diseases, Ninth and Tenth Revisions. Within this cohort, demographics, utilization, and cost were collected and analyzed using descriptive statistics and multivariable regression models.

Results:
6,325 records with GD diagnoses and GAS procedures were identified. From 2012-2019, utilization increased by more than 5-fold (0.9 to 5.0 per 100,000 records among all records), and the mean, inflation-adjusted cost increased by 36% ($19,451 to $26,517). This cost trend was similar by type of surgery, and genital surgery had consistently higher costs than chest surgery from 2012 to 2019 (genital: $21,487 to $26,712, chest: $13,238 to $21,309). Lower odds of utilization were found in records with Medicaid (OR = 0.27, 95% CI [0.22-0.35], P<0.001) and Medicare (OR = 0.15, 95% CI [0.11-0.23], P<0.001) compared to private insurance, as well as those in the lowest income quartile (OR = 0.68, 95% CI [0.54-0.85], P<0.001) compared to the highest quartile. Lower costs were found in records that indicated hospital location in the Midwest (27% lower, 95% CI [0.61-0.87], P<0.001), Northeast (34% lower, 95% CI [0.55-0.80], P<0.001) and South (39% lower, 95% CI [0.53-0.71], P<0.001) compared to the West.

Conclusions:
As demand for GAS increases with varying utilization and costs based on patient and hospital characteristics, there will likely be a need for more qualified surgeons, increased insurance coverage, and policies to ensure equitable access to GAS.
A Role For Electrocardiograms in Aortic Stenosis Screening: A Retrospective Trial
Authors: Pulaski Matthew , Newadkar Aditi , Richie Iman , Urnes Cole , Ho Ivan , Joseph Jubin , Matthews Ray , Zaman Junaid 
Published: April 2024

AbstractBackgroundAortic stenosis affects 1 in 50 adults over age 65 and is associated with significant morbidity and mortality. Machine learning has identified an association between right-sided precordial U waves and moderate to severe aortic stenosis. No study has explored the role of ECG screening by primary care physicians for patients with unknown aortic stenosis status.MethodsA retrospective single center cohort analysis performed by non-cardiologists identified right-sided precordial U waves on ECGs in fifty adults ages 65 to 89. Following identification, reviewers were unblinded to echocardiograms to determine whether there was an association between right-sided precordial U waves and aortic stenosis severity. Fifty age- and gender-matched patients without right-sided precordial U waves comprised the control group.ResultsChi-squared analysis revealed a significant association between right-sided precordial U waves and severity of aortic stenosis (χ2= 16.77, df = 3, p < 0.001). Multinomial logistic regressions demonstrated no relationship between categorical SBP (< 125, 126 – 145, > 145) and aortic stenosis (p = 0.35), but increasing categorical age (65-73, 74-81, 82-89) was associated with moderate to severe aortic stenosis (p = 0.002).ConclusionsOur data highlights right-sided precordial U wave identification by non-cardiologists as a novel objective adjunct to the physical examination in detection of a medical condition which portends significant morbidity and mortality if left untreated. These findings motivate a prospective randomized clinical trial in the utility of right-sided precordial U waves in screening for aortic stenosis in primary care settings.
Understanding the effect of pulse width on activation depth in TENS: A computational study
Authors: Guillen Alexander , Truong Dennis Q. , Cakmak Yusuf O. , Li Sheng , Datta Abhishek 
Published: April 2024

Background: Transcutaneous electrical nerve stimulation (TENS) has been a commonly used modality to relieve aches and pain for over 40 years. Commercially available devices provide multiple therapy modes involving a different combination of frequency and pulse width with intensity. While frequency sets sensation, intensity helps determine tolerability, longer pulse width is reported to induce a feeling of deeper stimulation. In fact, longer pulse width has been empirically shown to deliver current into deeper tissues, but in context of other electrical stimulation modalities. The goal of this study was to unpack the relationship between pulse width and activation depth in TENS. Methods: A highly realistic, anatomically-based, 3D finite element model of the forearm was used to simulate the electric field (E-field) distribution, as the pulse width is varied. A typical titration-guided mechanism was used to obtain the strength-duration (S-D) curves of a sensory McIntyre-Richardson-Grill (MRG) axonal model simulating the pain-transmitting A-delta fibers. The pulse widths tested ranged from 30 μs to 495 μs. Results: As expected, shorter pulse widths required more current to achieve activation, resulting in a larger E-field. The S-D curve of the target median nerve indicates a rheobase of 1.75 mA and a chronaxie of 232 µsec. When the applied currents are the same, shorter pulse widths result in a smaller volume of tissue activated (VTA) compared to the longer pulse widths. A 21 fold difference in VTA was found between the longest and shortest pulse widths considered. We observed a linear relationship between pulse width and activation depth for the conditions tested in the study. Conclusion: Our findings highlight the impact of pulse width on activation depth. While choice of a given therapy mode is usually based on an ad-hoc desirable sensation basis, medical professionals may consider advocating a certain therapy mode based on the depth of the intended target nerve.
“Mitigating Cancer Pain: What else Matters?”—A Qualitative Study into the Needs and Concerns of Cancer Patients in Sri Lanka
Authors: Edirisinghe NP , Makuloluwa PTR , Amarasekara AATD , Goonewardena CSE 
Published: April 2024

AbstractObjectivesThe overall experience of cancer pain reflects patients’ needs and concerns. Therefore, a thorough understanding of the patient’s needs and concerns is crucial to implementing satisfactory pain outcomes. This study aims to explore the needs and concerns of patients with cancer pain in Sri Lanka.MethodsThis study employed a descriptive qualitative approach among purposively selected patients with cancer and registered at the pain management unit. Patients eighteen years older with cancer-related pain were recruited. Noncancerous pain and those with psychological disorders, and brain metastases were excluded. Twenty-one semi-structured interviews were conducted until data saturation using a semi-structured interview guide, each lasting 30-60 minutes. Data were analyzed by Graneheim and Lundman’s content analysis method.ResultsThe study primarily involved participants aged 51-60 Sinhalese Buddhists. It highlighted two main themes: ‘Changes in normal lifestyle’ and ‘Needs and expectations’. The ‘Changes in normal lifestyle’ theme included subthemes like ‘Functional limitations’, ‘Emotional reactions’, ‘altered interpersonal relationships’, and ‘Socio-financial problems’. The ‘Needs and expectations’ theme covered desires for a ‘Pain-free life’, a return to a ‘Normal lifestyle’, and the ‘Need for a caregiver’. The findings emphasize that the most significant issue for cancer patients is the disruption to their normal lifestyle due to various challenges, while their primary need is to live without pain.Conclusions‘Life without pain’ is a cancer sufferer’s greatest need while ‘changes in normal lifestyle’ owing to bio-psycho-social-spiritual problems is their primary concern.
PIMMS-Dash: Accessible analysis, interrogation, and visualisation of high-throughput transposon insertion sequencing (TIS) data
Authors: Blanchard Adam M. , Taylor Adam , Warry Andrew , Shephard Freya , Curwen Alice , Leigh James A. , Emes Richard D. , Egan Sharon A. 
Published: April 2024

AbstractMotivationCurrent methods for visualising and interrogating high-throughput transposon insertion mutagenesis sequencing (TIS) data requires a significant time investment in learning bioinformatics, often producing static figures that do not facilitate real time analysis.SummaryWe have created an accessible web-based browser tool for visualisation and downstream analysis of high-throughput TIS data. This includes multiple interactive and sortable tables to aid the user to identify genes of interest, enabling the user to gain a greater understanding of the genes contributing to fitness in their experimental work. PIMMS-Dash permits researchers, with any level of bioinformatics knowledge, to interrogate data sets and generate publication quality figures.AvailabilityPIMMS-Dash is freely available and is accessible online athttps://pimms-dashboard-uon.azurewebsites.net
Globetrotting geckos: Historical biogeography suggests an Indian origin and “Out-Of-India” dispersal for the cosmopolitanHemidactylusgeckos
Authors: Agashe Madhura , Biswas Aritra , Karanth K. Praveen 
Published: April 2024

AimFollowing the breakup of Gondwana, dispersal events both into and out of India have influenced the biotic assembly of the surrounding landmasses. The cosmopolitanHemidactyluspresents an intriguing group to examine these instances, particularly given its sister relationship with the endemicDravidogeckofound in India’s Western Ghats. Despite earlier theories of Afro-Arabian or Southeast Asian origins forHemidactylus, its deep divergence fromDravidogecko(∼57 million years ago) suggests a potential Indian origin, thus contradicting an “Into-India” scenario proposed for the current Indian tetrapod groups. We thus aim to resolve the origins and shed light on the inter-continental dispersals inHemidactylusby reconstructing its biogeographic history.LocationWorldwideTaxonHemidactylusGeckosMethodsWe use six nuclear genes to reconstruct a reduced representation backbone phylogeny ofHemidactylususing likelihood, Bayesian, and coalescent based methods. We further assemble a timetree using a concatenated dataset of nuclear and mitochondrial markers from 132 of the 192Hemidactylusspecies by constraining the topology with the backbone phylogeny and secondary calibrations. We use this chronogram to reconstruct ancestral geographic ranges using BioGeoBEARS, employing a time-stratified approach in conjunction with plate tectonics information to explicitly test four hypotheses regarding the origin of the genus — An Indian origin, a Southeast Asian origin, a Saharo-Arabian origin, or an Afrotropical origin.ResultsOur findings suggest that the ancestral lineage ofHemidactylusandDravidogeckocolonized the drifting Indian plate from Southeast Asia approximately 57 million years ago, eventually evolving into the two genera in the Indian subcontinent. Following this,Hemidactylusdispersed multiple times from India to Africa and Asia.Main ConclusionThis study proposes an Indian origin for these widely distributed geckos, representing a rare instance of an “Out-of-India” dispersal scenario observed in a non-Gondwanan squamate group. Additionally, our research underscores the significance of incorporating sister taxa in biogeographic analyses to avoid misinterpretations of ancestral ranges.
A Re-Analysis of an ExistingDrosophila melanogasterDataset Reveals a New Set of Genes Involved in Post-Mating Response
Authors: Bennett Chloe J. , Aramayo Rodolfo 
Published: April 2024

ABSTRACTRNA sequencing (RNA-seq) is a commonly used method to identify changes in gene expression between two conditions. The analysis of RNA-seq output is complicated, with the possibility of getting different results from the same raw data. We developed and deployed four parallel pipelines to reanalyze an existing dataset of two femaleDrosophila melanogastertissue types before and after mating. TheDrosophilapost-mating response (PMR) is a well-characterized suite of changes that occur after mating, accompanied by a flux in gene expression. In comparing our study with the previous analysis of this dataset, we find our results to be more stringent, though we do identify a number of significant genes not found before. We also found variation among our own separate experiments, with gene-to-transcript isoform number and index building playing important roles in outcome. Finally, we identified a set of genes found by our pipeline that were not identified by the previous study and proposed potential roles for these genes in post-mating biology. Together, this work presents a critique of current RNA-seq analysis techniques and proposes multiple workflow adjustments that can increase the sensitivity, specificity, and stringency of differential gene expression studies.
Cross-platform proteomics signatures of extreme old age
Authors: Reed Eric R , Chandler Kevin B , Lopez Prisma , Costello Catherine E , Andersen Stacy L , Perls Thomas T , Li Mengze , Bae Harold , Soerensen Mette , Monti Stefano , Sebastiani Paola 
Published: April 2024

AbstractIn previous work we used a Somalogic platform targeting approximately 5000 proteins to generate a serum protein signature of centenarians that we validated in independent studies that used the same technology. We set here to validate and possibly expand the results by profiling the serum proteome of a subset of individuals included in the original study using liquid chromatography tandem mass spectrometry (LC-MS/MS). Following pre-processing, the LC-MS/MS data provided quantification of 398 proteins, with only 266 proteins shared by both platforms. At 1% FDR statistical significance threshold, the analysis of LC-MS/MS data detected 44 proteins associated with extreme old age, including 23 of the original analysis. To identify proteins for which associations between expression and extreme-old age were conserved across platforms, we performed inter-study conservation testing of the 266 proteins quantified by both platforms using a method that accounts for the correlation between the results. From these tests, a total of 80 proteins reached 5% FDR statistical significance, and 26 of these proteins had concordant pattern of gene expression in whole blood. This signature of 80 proteins points to blood coagulation, IGF signaling, extracellular matrix (ECM) organization, and complement cascade as important pathways whose protein level changes provide evidence for age-related adjustments that distinguish centenarians from younger individuals.
Sapling: Inferring and Summarizing Tumor Phylogenies from Bulk Data using Backbone Trees
Authors: Qi Yuanyuan , El-Kebir Mohammed 
Published: April 2024

AbstractCancer phylogenies are key to understanding tumor evolution. There exists many important downstream analyses that takes as input a single or small number of trees. However, due to uncertainty, one typically infers many, equally-plausible phylogenies from bulk DNA sequencing data of tumors. We introduce Sapling, a heuristic method to solve the Backbone Tree Inference from Reads problem, which seeks a small set of backbone trees on a smaller subset of mutations that collectively summarize the entire solution space. Sapling also includes a greedy algorithm to solve the Backbone Tree Expansion from Reads problem, which aims to expand an inferred backbone tree into a full tree. We prove that both problems are NP-hard. On simulated and real data, we demonstrate that Sapling is capable of inferring high-quality backbone trees that adequately summarize the solution space and that can expanded into full trees.