bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laser and Pelvic Floor Muscle Training for Urinary Incontinence: A Randomized Clinical Trial
Authors: Rocha-Rangel Samantha Conde , Pereira Gláucia Miranda Varella , Juliato Cassia Raquel Teatin , Brito Luiz Gustavo Oliveira 
Published: April 2024

Importance
Pelvic floor muscle training (PFMT) is considered the first option as a conservative treatment for female stress urinary incontinence (SUI). However, there is still debate whether energy-based devices are effective for treating SUI.

Objective
The objective of this study was to assess whether PFMT and fractional CO2 laser therapy may improve symptoms in women with SUI.

Study Design
A parallel, randomized, nonblinded, noninferiority trial included 94 of 144 women 18 years or older with SUI randomized into 2 groups. The CO2 laser group (n = 47) received 3 vaginal applications at monthly intervals. The PFMT group (n = 47) underwent 2 weekly sessions. Primary outcome was the mean difference of International Consultation on Incontinence Questionnaire—Urinary Incontinence Short-Form (ICIQ-UI-SF) total scores between groups after 3 and 6 months. Main secondary outcomes were questionnaires for assessment of pelvic floor symptoms (Pelvic Floor Impact Questionnaire—Short Form 7 [PFIQ-7]), sexual function (Female Sexual Function Index [FSFI]), and improvement after treatment (Patient Global Impression of Improvement [PGI-I]).

Results
A reduction in the ICIQ-UI-SF total score, PFIQ total score, and the Urinary Impact Questionnaire score was perceived between baseline and 3–6 months in both groups. CO2 laser did not reach the noninferiority margin when compared with PFMT in both follow-up periods and analyses. Pelvic floor muscle training has improved the FSFI desire domain between baseline and 3–6 months, whereas CO2 laser improved the FSFI orgasm, pain, and total score after 3 months and FSFI orgasm and total score after 6 months. PGI-I assessment has shown an improvement in both groups.

Conclusion
Fractional CO2 laser therapy was noninferior to PFMT after 3–6 months of treatment. Both groups presented a reduction in the ICIQ-UI-SF scores, and both methods could be considered for women with SUI.
Global Outcomes Benchmarks in Laparoscopic Liver Surgery for Segments 7 and 8: International Multicenter Analysis
Authors: Lopez-Lopez Victor , Morise Zeniche , Gomez Gavara Concepción , Gero Daniel , Abu Hilal Mohammed , Goh Brian KP , Herman Paulo , Clavien Pierre-Alain , Robles-Campos Ricardo , Wakabayashi Go ,   the Laparoscopic Liver Surgery Multicenter Study Group
Published: April 2024

BACKGROUND:
In recent years, there has been growing interest in laparoscopic liver resection (LLR) and the audit of the results of surgical procedures. The aim of this study was to define reference values for LLR in segments 7 and 8.

STUDY DESIGN:
Data on LLR in segments 7 and 8 between January 2000 and December 2020 were collected from 19 expert centers. Reference cases were defined as no previous hepatectomy, American Society of Anesthesiologists score less than 3, BMI less than 35 kg/m2, no chronic kidney disease, no cirrhosis and portal hypertension, no COPD (forced expiratory volume 1 <80%), and no cardiac disease. Reference values were obtained from the 75th percentile of the medians of all reference centers.

RESULTS:
Of 585 patients, 461 (78.8%) met the reference criteria. The overall complication rate was 27.5% (6% were Clavien-Dindo 3a or more) with a mean Comprehensive Complication Index of 7.5 ± 16.5. At 90-day follow-up, the reference values for overall complication were 31%, Clavien-Dindo 3a or more was 7.4%, conversion was 4.4%, hospital stay was less than 6 days, and readmission rate was <8.33%. Patients from Eastern centers categorized as low risk had a lower rate of overall complication (20.9% vs 31.2%, p = 0.01) with similar Clavien-Dindo 3a or more (5.5% and 4.8%, p = 0.83) compared with patients from Western centers, respectively.

CONCLUSIONS:
This study shows the need to establish standards for the postoperative outcomes in LLR based on the complexity of the resection and the location of the lesions.
Prospective Outpatient Follow-Up of Early Cognitive Impairment in Patients with Mild Traumatic Brain Injury and Intracranial Hemorrhage
Authors: Jebbia Mallory , Stopenski Stephen , Grigorian Areg , Kuza Catherine , Bloom Samuel , Rao Pranthi , Alvarez Claudia , Dolich Matthew , Nguyen Ninh , Nahmias Jeffry 
Published: April 2024

BACKGROUNG:
Mild traumatic brain injury (mTBI) encompasses a spectrum of disability including early cognitive impairment (ECI). The Brain Injury Guidelines suggest that patients with mTBI can be safely discharged from the emergency department. Although half of patients with mTBI with intracranial hemorrhage (ICH) have evidence of ECI, it is unclear what percentage of these patients’ ECI persists after discharge. We hypothesize a significant proportion of trauma patients with mTBI and ECI at presentation have persistent ECI at 30-day follow-up.

STUDY DESIGN:
A single-center prospective cohort study including adult trauma patients with ICH or skull fracture and a Glasgow Coma Scale of 13 to 15 on arrival was performed. Participants were screened for ECI using the Rancho Los Amigos Scale (RLA), and ECI was defined as an RLA less than 8. We compared ECI and non-ECI groups for demographics, injury profile, CT imaging (eg Rotterdam CT score) and outcomes with bivariate analysis. Thirty-day follow-up telephone calls were performed to re-evaluate RLA for persistent ECI and concussion symptoms.

RESULTS:
From 62 patients with ICH or skull fracture and mTBI, 21 (33.9%) had ECI. Patients with ECI had a higher incidence of subarachnoid hemorrhage (85.7% vs 46.3%, p = 0.003) and higher Rotterdam CT score (p = 0.004) compared with those without ECI. On 30-day follow-up, 6 of 21 (26.6%) patients had persistent ECI. In addition, 7 (33.3%) patients had continued concussion symptoms.

CONCLUSIONS:
More than one-third of mTBI patients with ICH had ECI. At 30-day postdischarge follow-up, more than one-fourth of these patients had persistent ECI and 33% had concussion symptoms. This highlights the importance of identifying ECI before discharge as a significant portion may have ongoing difficulties reintegrating into work and society.
Global review of meta-analyses reveals key data gaps in agricultural impact studies on biodiversity in croplands
Authors: Bonfanti Jonathan , Langridge Joseph , Avadí A. , Casajus N. , Chaudhary A. , Damour G. , Estrada-Carmona N. , Jones S. K. , Makowski D. , Mitchell M. , Seppelt R. , Beillouin Damien 
Published: April 2024

AbstractAimAgriculture depends heavily on biodiversity, yet unsustainable management practices continue to affect a wide range of organisms and ecosystems at unprecedented levels worldwide. Addressing the global challenge of biodiversity loss requires access to consolidated knowledge across management practices, spatial levels, and taxonomic groups.LocationGlobalTime period1994 to 2022Major taxa studiedAnimals, microorganisms, plants.MethodsWe conducted a comprehensive literature review synthesising data from all meta-analyses about the impacts of agricultural management practices on biodiversity in croplands, covering field, farm, and landscape levels. From 200 retained meta-analyses, we extracted 1,885 mean effect sizes (from 69,850 comparisons between a control and treatment) assessing the impact of management practices on biodiversity, alongside characterising over 9,000 primary papers.ResultsSeven high-income countries, notably the USA, China, and Brazil dominate agricultural impact studies with fertiliser use, phytosanitary interventions and crop diversification receiving widespread attention. The focus on individual practices overshadows research at the farm and landscape level. Taxonomically, Animalia, especially arthropods, are heavily studied while taxa such as annelids and plants receive comparatively less attention. Effect sizes are predominantly calculated from averaged abundance data. Significant gaps persist in terms of studies on the effects of agricultural interventions on specific taxonomic groups (e.g. annelids, mammals) and studies analysing functional traits.Main conclusionsOur study highlights the importance of analysing the effects of combined practices to accurately reflect real-world farming contexts. While abundance metrics are common, reflecting several biodiversity facets and adopting a more balanced research approach across taxa are crucial for understanding biodiversity responses to agricultural changes and informing conservation strategies. Given the unbalanced evidence on impacts of agricultural practices on biodiversity, caution is required when utilising meta-analytical findings for informing public policies or integrating them into global assessment models like life-cycle assessments or global flux models.
Late-Stage Skeletal Muscle Transcriptome in Duchenne muscular dystrophy shows a BMP4-Induced Molecular Signature
Authors: Sothers Hanna , Hu Xianzhen , Crossman David K. , Si Ying , Alexander Matthew S. , McDonald Merry-Lynn N. , King Peter H. , Lopez Michael A. 
Published: April 2024

AbstractDuchenne muscular dystrophy (DMD) is a fatal X-linked recessive disease due to loss-of-function mutations in theDYSTROPHINgene. DMD-related skeletal muscle wasting is typified by an aberrant immune response involving upregulation of TGFβ family of cytokines. We previously demonstrated that bone morphogenetic protein 4 (BMP4) is increased in DMD and BMP4 stimulation induces a 20-fold upregulation ofSmad8transcription. However, the role of BMP4 in severely affected DMD skeletal muscle is unknown. We hypothesized that transcriptomic signatures in severely affected human DMD skeletal muscle are driven by BMP4 signaling. Transcriptomes from skeletal muscle biopsies of late-stage DMD vs. non-DMD controls and C2C12 muscle cells with or without BMP4 stimulation were generated by RNA-Seq and analyzed for single transcript differential expression as well as by Ingenuity Pathway Analysis and weighted gene co-expression network analyses. A total of 2,328 and 5,291 transcripts in the human muscle and C2C12 muscle cells, respectively, were differentially expressed. We identified an overlapping molecular signature of 1,027 genes dysregulated in DMD muscle that were induced in BMP4-stimulated C2C12 muscle cells. Highly upregulated DMD transcripts that overlapped with BMP4-stimulated C2C12 muscle cells includedADAMTS3, HCAR2, SERPING1, SMAD8, andUNC13C.The DMD transcriptome was characterized by dysregulation of pathways involving immune function, extracellular matrix remodeling, and metabolic/mitochondrial function. In summary, we define a late-stage DMD skeletal muscle transcriptome that substantially overlaps with the BMP4-induced molecular signature in C2C12 muscle cells. This supports BMP4 as a disease-driving regulator of transcriptomic changes in late-stage DMD skeletal muscle and expands our understanding of the evolution of dystrophic signaling pathways and their associated gene networks that could be explored for therapeutic development.
Lysosome-acidifying nanoparticles rescue A30P α-synuclein induced neuronal death in cellular andDrosophilamodels of Parkinson’s disease
Authors: Lo Chih Hung , Ren Mengda , Loi Gavin Wen Zhao , Saipuljumri Eka Norfaishanty , Indajang Jonathan , Lim Kah Leong , Zeng Jialiu 
Published: April 2024

AbstractParkinson’s disease (PD) is an age-related neurodegenerative disease characterized by histopathological hallmarks of Lewy bodies formed by accumulation of α-synuclein (αSyn) and progressive loss of dopaminergic neurons in the substantia nigrapars compactaof the midbrain, with clinical symptoms of motor deficits. Toxic protein accumulation of αSyn in PD is associated with autolysosomal acidification dysfunction that contributes to defective autophagy-lysosomal degradation system. While lysosome-acidifying nanoparticles have been applied as therapeutics to ameliorate dopaminergic neurodegeneration in neurotoxin mediated or αSyn aggregates induced mouse model of sporadic PD, lysosome-targeted approach has not yet been applied in synucleinopathy models of familial PD. Here, we report the first application of the new poly(ethylene tetrafluorosuccinate-co-succinate) (PEFSU)-based acidic nanoparticles (AcNPs) in A30P αSyn overexpressing SH-SY5Y cells andDrosophilamodels of PD. In the cellular model, we showed that AcNPs restore lysosomal acidification, promote autophagic clearance of αSyn, improve mitochondrial turnover and function, and rescue A30P αSyn induced death in SH-SY5Y cells. In theDrosophilamodel, we demonstrated that AcNPs enhance clearance of αSyn and rescue dopaminergic neuronal loss in fly brains and improve their locomotor activity. Our results highlight AcNPs as a new class of lysosome-acidifying therapeutic for treatment of PD and other proteinopathies in general.
Spherical Phenotype Clustering
Authors: Nightingale Luke , Tuersley Joseph , Cairoli Andrea , Howes Jacob , Shand Cameron , Powell Andrew , Green Darren , Strange Amy , Warchal Scott , Howell Michael 
Published: April 2024

AbstractPhenotypic screening experiments comprise many images of the same cells perturbed in different ways, with biologically significant variation often subtle or difficult to see by eye. The specialized nature of the morphological changes and the fact that large quantities of data can be produced quickly makes training new machine learning models attractive. A byproduct of the experimental setup is knowledge of which well an image originated from and the treatment applied. We propose a geometrically inspired variant of contrastive learning incorporating this metadata. The method is tested on the BBBC021 benchmark dataset and in datasets of HaCaT cells perturbed chemically or genetically. On BBBC021 we attain higher NSC and NSCB scores than existing unsupervised (or weakly supervised) methods. In the HaCaT cells we find consistent quantitative gains and qualitative clustering reflecting underlying biology, including alignment of chemical and genetic perturbations.
Dzip1 is dynamically expressed in the vertebrate germline and regulates the development ofXenopusprimordial germ cells
Authors: Turgeon Aurora , Fu Jia , Divyanshi  , Ma Meng , Jin Zhigang , Hwang Hyojeong , Li Meining , Qiao Huanyu , Mei Wenyan , Yang Jing 
Published: April 2024

AbstractPrimordial germ cells (PGCs) are the precursors of sperms and oocytes. Proper development of PGCs is crucial for the survival of the species. In many organisms, factors responsible for PGC development are synthesized during early oogenesis and assembled into the germ plasm. During early embryonic development, germ plasm is inherited by a few cells, leading to the formation of PGCs. While germline development has been extensively studied, how components of the germ plasm regulate PGC development is not fully understood. Here, we report that Dzip1 is dynamically expressed in vertebrate germline and is a novel component of the germ plasm inXenopusand zebrafish. Knockdown of Dzip1 impairs PGC development inXenopusembryos. At the molecular level, Dzip1 physically interacts with Dazl, an evolutionarily conserved RNA-binding protein that plays a multifaced role during germline development. We further showed that the sequence between amino acid residues 282 and 550 of Dzip1 is responsible for binding to Dazl. Disruption of the binding between Dzip1 and Dazl leads to defective PGC development. Taken together, our results presented here demonstrate that Dzip1 is dynamically expressed in the vertebrate germline and plays a novel function duringXenopusPGC development.
Models optimized for real-world tasks reveal the task-dependent necessity of precise temporal coding in hearing
Authors: Saddler Mark R. , McDermott Josh H. 
Published: April 2024

ABSTRACTNeurons encode information in the timing of their spikes in addition to their firing rates. Spike timing is particularly precise in the auditory nerve, where action potentials phase lock to sound with sub-millisecond precision, but its behavioral relevance remains uncertain. We optimized machine learning models to perform real-world hearing tasks with simulated cochlear input, assessing the precision of auditory nerve spike timing needed to reproduce human behavior. Models with high-fidelity phase locking exhibited more human-like sound localization and speech perception than models without, consistent with an essential role in human hearing. However, the temporal precision needed to reproduce human-like behavior varied across tasks, as did the precision that benefited real-world task performance. These effects suggest that perceptual domains incorporate phase locking to different extents depending on the demands of real-world hearing. The results illustrate how optimizing models for realistic tasks can clarify the role of candidate neural codes in perception.
Mind the gap: the relevance of the genome reference to resolve rare and pathogenic inversions
Authors: Bilgrav Saether Kristine , Eisfeldt Jesper , Bengtsson Jesse , Lun Ming Yin , Grochowski Christopher M. , Mahmoud Medhat , Chao Hsiao-Tuan , Rosenfeld Jill A. , Liu Pengfei , Schuy Jakob , Ameur Adam ,   Undiagnosed Diseases Network, Hwang James Paul , Sedlazeck Fritz J. , Bi Weimin , Marom Ronit , Nordgren Ann , Carvalho Claudia M.B. , Lindstrand Anna 
Published: April 2024

AbstractBoth long-read genome sequencing (lrGS) and the recently published Telomere to Telomere (T2T) reference genome provide increased coverage and resolution across repetitive regions promising heightened structural variant detection and improved mapping. Inversions (INV), intrachromosomal segments which are rotated 180° and inserted back into the same chromosome, are a class of structural variants particularly challenging to detect due to their copy-number neutral state and association with repetitive regions. Inversions represent about 1/20 of all balanced structural chromosome aberrations and can lead to disease by gene disruption or altering regulatory regions of dosage sensitive genesin cis.Here we remapped the genome data from six individuals carrying unsolved cytogenetically detected inversions. An INV6 and INV10 were resolved using GRCh38 and T2T-CHM13. Finally, an INV9 required optical genome mapping,de novoassembly of lrGS data and T2T-CHM13. This inversion disrupted intron 25 ofEHMT1,confirming a diagnosis of Kleefstra syndrome 1 (MIM#610253).These three inversions, only mappable in specific references, prompted us to investigate the presence and population frequencies of differential reference regions (DRRs) between T2T-CHM13, GRCh37, GRCh38, the chimpanzee and bonobo, and hundreds of megabases of DRRs were identified.Our results emphasize the significance of the chosen reference genome and the added benefits of lrGS and optical genome mapping in solving rearrangements in challenging regions of the genome. This is particularly important for inversions and may impact clinical diagnostics.
Robust prediction of relative binding energies for protein-protein complex mutations using free energy perturbation calculations
Authors: Sampson Jared M. , Cannon Daniel A. , Duan Jianxin , Epstein Jordan C. K. , Sergeeva Alina P. , Katsamba Phinikoula S. , Mannepalli Seetha M. , Bahna Fabiana A. , Adihou Hélène , Guéret Stéphanie M. , Gopalakrishnan Ranganath , Geschwindner Stefan , Rees D. Gareth , Sigurdardottir Anna , Wilkinson Trevor , Dodd Roger B. , De Maria Leonardo , Mobarec Juan Carlos , Shapiro Lawrence , Honig Barry , Buchanan Andrew , Friesner Richard A. , Wang Lingle 
Published: April 2024

AbstractComputational free energy-based methods have the potential to significantly improve throughput and decrease costs of protein design efforts. Such methods must reach a high level of reliability, accuracy, and automation to be effectively deployed in practical industrial settings in a way that impacts protein design projects. Here, we present a benchmark study for the calculation of relative changes in protein-protein binding affinity for single point mutations across a variety of systems from the literature, using free energy perturbation (FEP+) calculations. We describe a method for robust treatment of alternate protonation states for titratable amino acids, which yields improved correlation with and reduced error compared to experimental binding free energies. Following careful analysis of the largest outlier cases in our dataset, we assess limitations of the default FEP+ protocols and introduce an automated script which identifies probable outlier cases that may require additional scrutiny and calculates an empirical correction for a subset of charge-related outliers. Through a series of three additional case study systems, we discuss how protein FEP+ can be applied to real-world protein design projects, and suggest areas of further study.Graphical AbstractHighlightsReliable calculation of relative binding free energy changes for most protein mutations to within ∼1 kcal/mol.Automated Protein FEP+ Groups treatment of alternate protonation states for titratable residues.Application of FEP+ methodology to “real-world” protein design projects.
Cortical tracking of hierarchical rhythms orchestrates the multisensory processing of biological motion
Authors: Shen Li , Li Shuo , Tian Yuhao , Wang Ying , Jiang Yi 
Published: April 2024

AbstractWhen observing others’ behaviors, we continuously integrate their movements with the corresponding sounds to enhance perception and develop adaptive responses. However, how the human brain integrates these complex audiovisual cues based on their natural temporal correspondence remains unclear. Using electroencephalogram (EEG), we demonstrated that rhythmic cortical activity tracked the hierarchical rhythmic structures in audiovisually congruent human walking movements and footstep sounds. Remarkably, the cortical tracking effects exhibit distinct multisensory integration modes at two temporal scales: an additive mode in a lower-order, narrower temporal integration window (step-cycle) and a super-additive enhancement in a higher-order, broader temporal window (gait-cycle). Furthermore, while neural responses at the lower-order timescale reflect a domain-general audiovisual integration process, cortical tracking at the higher-order timescale is exclusively engaged in the integration of biological motion cues. In addition, only this higher-order, domain-specific cortical tracking effect correlates with individuals’ autistic traits, highlighting its potential as a neural marker for autism spectrum disorder. These findings unveil the multifaceted mechanism whereby rhythmic cortical activity supports the multisensory integration of human motion, shedding light on how neural coding of hierarchical temporal structures orchestrates the processing of complex, natural stimuli across multiple timescales.