bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Superficial and Functional Lymphatic Anatomy of the Upper Extremity
Authors: Granoff Melisa D. , Pardo Jaime , Johnson Anna Rose , Fleishman Aaron , Tillotson Elizabeth , Thomson Sarah , Lee Bernard T. , Singhal Dhruv 
Published: August 2022

Background:
Knowledge of detailed lymphatic anatomy in humans is limited as the small size of lymphatic channels makes it difficult to image. Most current knowledge of the superficial lymphatic system has been obtained from cadaveric dissections.

Methods:
Indocyanine green (ICG) lymphography was performed pre-operatively to map the functional arm lymphatics in breast cancer patients without clinical or objective evidence of lymphedema. A retrospective review was performed to extract demographic, ICG imaging, and surgical data.

Results:
Three main functional forearm channels with variable connections to two upper arm pathways were identified. The median forearm channel predominantly courses in the volar forearm (99%). The ulnar forearm channel courses in the volar forearm in the majority of patients (66%). The radial forearm channel courses in the dorsal forearm in the majority of patients (92%). Median (100%), radial (91%), and ulnar (96%) channels almost universally connect to the medial upper arm channel. In contrast, connections to the lateral upper arm channel occur less frequently from the radial (40%) and ulnar (31%) channels.

Conclusions:
This study details the anatomy of three forearm lymphatic channels and their connections to the upper arm in living adults without lymphatic disease. Knowledge of these pathways and variations is relevant to any individual performing procedures on the upper extremities as injury to the superficial lymphatic system can predispose patients to the development of lymphedema.
Informed Consent Practices in Global Surgery among Plastic Surgery Organizations
Authors: Thadikonda Kishan , Zhang Rosaline , Bruhn Jonathan , Nguyen Phuong D. , Poore Samuel O. 
Published: August 2022

Background:
Global surgery organizations often serve vulnerable and complex patient populations, but there is limited knowledge on the protocols used to obtain informed consent for procedures and content sharing.

Methods:
The Plastic Surgery Foundation Volunteers in Plastic Surgery (VIPS) database was queried for organizations actively involved in global surgery. Seventy-nine organizations received email invitations to participate in a survey study regarding their protocols for obtaining consent for procedures and sharing multimedia content.

Results:
A total of 17 (22% yield) organizations completed the survey. All were active for at least 10 years and 88% (15/17) organized at least two mission trips annually. Eighty-eight percent (15/17) reported obtaining written consent for surgical procedures. Less than half (46%, 8/17) of used a written consent form that was created jointly with the local hospital. For sharing content related to global surgery experiences, 75% (12/16) obtained some form of written consent while 6% (1/16) did not routinely obtain any consent. Organizations shared content most commonly through their websites and Facebook. All organizations reported using interpreters to obtain informed consent at least some of the time. 62% (10/16) reported that they relied primarily on volunteers or community members to provide informal interpretation assistance, rather than formally trained professional interpreters.

Conclusion:
Practices related to obtaining informed consent vary widely among global surgery organizations. The development of standardized protocols and guidelines will ensure that global health organizations, in collaboration with their local partners, properly obtain informed consent for procedures and sharing publicly viewable content.
The Superthin Profunda artery perforator flap for Extremity Reconstruction: Clinical Implications
Authors: Chim Harvey 
Published: August 2022

Background:
The profunda artery perforator (PAP) flap has numerous advantages. For coverage of extremity wounds, however, traditional subfascial harvest results in a thick flap, which routinely requires secondary thinning. The aim of this study was to describe our approach and experience with the thin and superthin PAP flap for extremity reconstruction.

Methods:
Using an approach of preoperative perforator localization with computed tomography angiogram (CTA), color and handheld doppler, we describe our experience with thin/ superthin PAP flaps using a single dominant perforator, for extremity reconstruction in 10 consecutive patients.

Results:
Mean age of patients who had a thin or superthin PAP flap for extremity reconstruction was 41.2 ± 21.3 years. Flaps were performed to cover wounds in the upper (n=3) and lower (n=7) extremities. Mean flap thickness was 0.7 ± 0.2 cm. Mean flap artery diameter was 16 ± 3 mm, mean flap vein diameter was 21 ± 6 mm. Mean pedicle length was 6.8 ± 1.2 cm. The difference between the actual measured intraoperative proximal-distal distance and the preoperative CTA measurement for each patient was calculated, with a mean difference of 1.2 ± 0.6 cm.

Conclusions:
Advantages of the PAP flap include a concealed donor site, large perforator caliber, long pedicle length and a straightforward perforator dissection. Intraoperative measurement of the proximal-distal distance of the dominant perforator fell within 2 cm of the preoperative CTA measurement in all cases. The thin and superthin PAP flap provides a new reconstructive option, particularly suited for use in the extremities.
“A Rectoprostatic Fascia Reinforcement Flap for the Treatment of Intraoperative Rectal Injury and Recto-Neovaginal Fistula in Gender Affirmation Surgery for Trans Women.”
Authors: Pansritum Kamol , Thomrongdullaphak Sarinthorn , Suwajo Poonpissamai 
Published: August 2022

Background:
Intraoperative rectal injuries and recto-neovaginal fistulas are rare complications in gender affirmation surgery for trans women. Primary repair with an improper method may result in recurrence. The procedures required for the surgical treatment of these problems are rare. We herein describe the surgical technique using a rectoprostatic fascia reinforcement flap for intraoperative rectal injury and recto-neovaginal fistula correction in gender affirmation surgery for trans women.

Methods:
Retrospective data were collected on the female transgender patients underwent surgical treatment of intraoperative rectal injury and rectovaginal fistula with the prostaticovesicular fascia reinforcement flap. Patient demographics, follow-up, and intraoperative details were collected and analyzed.

Results:
From January 2006 to December 2018, 14 female transgender patients presented with intraoperative rectal injuries and 5 cases of rectovaginal fistulas from a total of 2,059 patients who underwent neovaginoplasty. Two patients with rectovaginal fistulas had their neovaginoplasty performed elsewhere. The mean location of intraoperative rectal injury was 5.2 cm (2-6.5 cm) and the recto-neovaginal fistula was 5.4 cm (3.5-6.5 cm) from the vaginal introitus. The mean size of intraoperative rectal injury and recto-neovaginal fistula was 2.5 cm (1-3.5 cm) and 2.3 cm (0.2-3.2 cm) in diameter, respectively. No recurrence of rectovaginal fistulas was reported after one-year follow-up.

Conclusions:
A rectoprostatic fascia reinforcement flap is an alternative technique to repair intraoperative rectal injury and recto-neovaginal fistulas incorporating the neovaginal lining with a skin graft or sigmoid colon in gender affirmation surgery for trans women.
Intentional gesturing increases social complexity by allowing recipient's understanding of intentions when it is inhibited by stress
Authors: Roberts Anna Ilona , Roberts Sam George Bradley 
Published: August 2022

Examining the links between intentional communication and social relationships provides insights into the cognitive skills needed to manage a differentiated set of social bonds. Great apes gesture intentionally, but how this intentionality relates to sociality is still unclear. Stress in the form of dominant audience members inhibits understanding of intentions, downgrading cognition to understanding of behaviour, but intentional communication may enable social bonding in stressful conditions. We examined the associations between gestural communication, sociality, stress and the outcome of interactions in wild chimpanzees. Social network size was positively associated with intentional but not non-intentional communication. When a dominant bystander was present with whom the recipient was weakly bonded, and gesturing was non-intentional, recipients produced avoidance response toward signallers to whom they were weakly bonded, indicating understanding of behaviour. Signallers used intentional gestures more frequently to recipients who were stressed, and intentional gestures evoked approach behaviour by the recipients, indicating understanding of intentionality. These results suggest that the presence of dominant bystanders is stressful, inhibiting understanding of intentionality. However, intentional gestures facilitate social bonding by allowing understanding of intentions. The cognitive skills underpinning intentional gestures may therefore play a key role in enabling primates to meet the demands of sociality.
This article is part of the theme issue ‘Cognition, communication and social bonds in primates’.
Flexible signalling strategies by victims mediate post-conflict interactions in bonobos
Authors: Heesen Raphaela , Austry Diane A. , Upton Zoe , Clay Zanna 
Published: August 2022

Compared to other animals, humans supposedly excel at voluntarily controlling and strategically displaying emotional signals. Yet, new data shows that nonhuman great apes' emotion expressions may also be subject to voluntary control. A key context to further explore this is during post-conflict (PC) periods, where signalling by distressed victims may influence bystander responses, including the offering of consolation. To address this, our study investigates the signalling behaviour of sanctuary-living bonobo victims following aggression and its relation to audience composition and PC interactions. Results show that the production of paedomorphic signals by victims (regardless of age) increased their chances of receiving consolation. In adults, the production of such signals additionally reduced the risk of renewed aggression from opponents. Signal production also increased with audience size, yet strategies differed by age: while immatures reduced signalling in proximity of close-social partners, adults did so especially after receiving consolation. These results suggest that bonobos can flexibly adjust their emotion signalling to influence the outcome of PC events, and that this tendency has a developmental trajectory. Overall, these findings highlight the potential role that flexible emotion communication played in the sociality of our last common ancestor withPan.This article is part of the theme issue ‘Cognition, communication and social bonds in primates’.
A Novel Three-way fusion image segmentation for early esophageal cancer detection
Authors: Ren Xintong , Zhang Zhen , Jiang Junchao , Li Guodong , Jiang Jiahua , Ren Wuwei , Jia Xinyong 
Published: August 2022

AbstractObjectiveEsophageal cancer (EC) is a prevalent malignancy worldwide. Early-stage esophageal cancer (EEC) diagnostics is crucial for improving patient survival. However, EC is highly aggressive with a poor prognosis, even for experienced endoscopists. To address these problems, this study aims to develop a novel computer-aided diagnosis (CAD) method to improve the accuracy and efficiency of EEC diagnostics.MethodsThree-way fusion CAD method that employs multiple frameworks, including the hybrid task cascade ResNeXt101 with deformable convolutional networks, to accurately detect EC. Our method incorporates dual annotation categories on ME-NBI imaging from a local perspective and one category on LCE imaging from an broader perspective. This integration provides a substantial improvement of accuracy over traditional CAD technologies.ResultsOur three-way fusion CAD method achieved top performances of 0.923 mAP on ME-NBI and 0.862 mAP on LCE, demonstrating superior diagnostic performance compared to traditional CAD methods. Furthermore, the treatment boundary mAP is expected to be even higher by definition in clinical settings. Our method also achieved promising precision and recall rates of 93.98% and 93.05% for ME-NBI, and 82.89% and 88.32% for LCE, respectively.ConclusionsOur novel three-way fusion CAD method accurately detects EC in both ME-NBI and LCE imaging, providing accurate treatment boundaries on both image and patient levels. Our approach shows potential for clinical application, with promising mAP, precision, and recall rates. Further work will focus on collecting and analyzing patient data to improve the method’s real-time performance in clinical settings.
A sagittal gradient of pathological and compensatory effects of neurophysiological slowing in Parkinson’s disease
Authors: Wiesman Alex I. , da Silva Castanheira Jason , Degroot Clotilde , Fon Edward A. , Baillet Sylvain ,   PREVENT-AD Research Group,   Quebec Parkinson Network
Published: August 2022

AbstractUsing magnetoencephalographic imaging and extensive clinical and neuropsychological assessments, we show that patients with Parkinson’s disease (PD; N = 79) exhibit a slowing of neurophysiological activity relative to healthy adults (N = 65), which relates to motor and cognitive abilities. Importantly, the association between neurophysiological slowing and PD clinical features varies systematically across the cortex along a sagittal gradient: cortical slowing is associated with worse impairment in dorsal-posterior cortices, and this association is reversed in ventral-anterior cortical regions. This pathological-to- compensatory anatomical gradient is sensitive to differences in patients’ individual clinical profiles, and co- localizes with normative atlases of neurotransmitter receptor/transporter density. Long-range functional connectivity between posterior regions and parietal and frontal cortices is also significantly shifted towards lower frequencies in PD, demonstrating a novel network-level slowing effect. Taken together, these findings demonstrate the multifaceted nature of neurophysiological slowing in patients with PD, with anatomically-dependent clinical relevance to motor and cognitive symptoms.
Plasmodesmata-located proteins regulate plasmodesmal function at specific cell interfaces in Arabidopsis
Authors: Li Zhongpeng , Liu Su-Ling , Montes-Serey Christian , Walley Justin W. , Aung Kyaw 
Published: August 2022

AbstractPlasmodesmata (PD) are membrane-lined channels connecting adjoining plant cells. PD control symplasmic intercellular communication by allowing molecules to move between cells. Plant polysaccharide callose (ß-1,3-glucan) is deposited at PD, affecting plasmodesmal function; however, the regulation of PD at different cell interfaces is largely unknown. This study discovered that two PD-located proteins, PDLP5 and PDLP6, are expressed in non-overlapping cell types. The constitutive expression of PDLP5 and PDLP6 results in the overaccumulation of PD callose at different cell interfaces and starch hyperaccumulation in different cell types within mature leaves. Using a proximity labeling approach, we identified sucrose synthase 6 (SUS6) as a functional partner of PDLP6. We further demonstrated that PDLP6 physically and genetically interacts with SUS6. In addition, callose synthase 7 (CalS7) interacts with both SUS6 and PDLP6 and is required for PDLP6’s function. We propose that PDLP6-SUS6-CalS7 forms a callose synthase complex in the vasculature to regulate the plasmodesmal function.
The evolution of two transmissible leukaemias colonizing the coasts of Europe
Authors: Bruzos Alicia L. , Santamarina Martín , García-Souto Daniel , Díaz Seila , Rocha Sara , Zamora Jorge , Lee Yunah , Viña-Feás Alejandro , Quail Michael A. , Otero Iago , Pequeño-Valtierra Ana , Temes Javier , Rodriguez-Castro Jorge , Villanueva Antonio , Costas Damián , Rodríguez Rosana , Prieto Tamara , Tomás Laura , Alvariño Pilar , Alonso Juana , Cao Asunción , Iglesias David , Carballal María J. , Amaral Ana M. , Balseiro Pablo , Calado Ricardo , El Khalfi Bouchra , Izagirre Urtzi , de Montaudouin Xavier , Pade Nicolas G. , Probert Ian , Ricardo Fernando , Ruiz Pamela , Skazina Maria , Smolarz Katarzyna , Pasantes Juan J. , Villalba Antonio , Ning Zemin , Ju Young Seok , Posada David , Demeulemeester Jonas , Baez-Ortega Adrian , Tubio Jose M. C. 
Published: August 2022

AbstractTransmissible cancers are malignant cell clones that spread among individuals through transfer of living cancer cells. Several such cancers, collectively known as bivalve transmissible neoplasia (BTN), are known to infect and cause leukaemia in marine bivalve molluscs. This is the case of BTN clones affecting the common cockle,Cerastoderma edule, which inhabits the Atlantic coasts of Europe and north-west Africa. To investigate the origin and evolution of contagious cancers in common cockles, we collected 6,854C. edulespecimens and diagnosed 390 cases of BTN. We then generated a reference genome for the species and assessed genomic variation in the genomes of 61 BTN tumours. Analysis of tumour-specific variants confirmed the existence of two cockle BTN lineages with independent clonal origins, and gene expression patterns supported their status as haemocyte-derived marine leukaemias. Examination of mitochondrial DNA sequences revealed several mitochondrial capture events in BTN, as well as co-infection of cockles by different tumour lineages. Mutational analyses identified two lineage-specific mutational signatures, one of which resembles a signature associated with DNA alkylation. Karyotypic and copy number analyses uncovered genomes marked by pervasive instability and polyploidy. Whole-genome duplication, amplification of oncogenesCCND3andMDM2, and deletion of the DNA alkylation repair geneMGMT, are likely drivers of BTN evolution. Characterization of satellite DNA identified elements with vast expansions in the cockle germ line, yet absent from BTN tumours, suggesting ancient clonal origins. Our study illuminates the evolution of contagious cancers under the sea, and reveals long-term tolerance of extreme instability in neoplastic genomes.
A yeast-based system to study SARS-CoV-2 Mpro structure and to identify nirmatrelvir resistant mutations
Authors: Ou Jin , Lewandowski Eric M. , Hu Yanmei , Lipinski Austin A. , Morgan Ryan T. , Jacobs Lian M.C. , Zhang Xiujun , Bikowitz Melissa J. , Langlais Paul , Tan Haozhou , Wang Jun , Chen Yu , Choy John S. 
Published: August 2022

AbstractThe SARS-CoV-2 main protease (Mpro) is a major therapeutic target. The Mpro inhibitor, nirmatrelvir, is the antiviral component of Paxlovid, an orally available treatment for COVID-19. As Mpro inhibitor use increases, drug resistant mutations will likely emerge. We have established a non-pathogenic system, in which yeast growth serves as a proxy for Mpro activity, enabling rapid identification of mutants with altered enzymatic activity and drug sensitivity. The E166 residue is known to be a potential hot spot for drug resistance and yeast assays showed that an E166R substitution conferred strong nirmatrelvir resistance while an E166N mutation compromised activity. On the other hand, N142A and P132H mutations caused little to no change in drug response and activity. Standard enzymatic assays confirmed the yeast results. In turn, we solved the structures of Mpro E166R, and Mpro E166N, providing insights into how arginine may drive drug resistance while asparagine leads to reduced activity. The work presented here will help characterize novel resistant variants of Mpro that may arise as Mpro antivirals become more widely used.
CSL-Tox: An open-source analytical framework for the comparison of short-term and long-term toxicity end points and exploring the opportunities for decreasing in-vivo studies conducted for drug development programs
Authors: Naga Doha , Dimitrakopoulou Smaragda , Roberts Sonia , Husar Elisabeth , Mohr Susanne , Booler Helen , Musvasva Eunice 
Published: August 2022

AbstractIn-vivo toxicity assessment is an important step prior to clinical development and is still the main source of data for overall risk assessment of a new molecular entity (NCE). All in-vivo studies are performed according to regulatory requirements and many efforts have been exerted to minimize these studies in accordance with the (Replacement, Reduction and Refinement) 3Rs principle. Many aspects of in-vivo toxicology packages can be optimized to reduce animal use, including the number of studies performed as well as study durations, which is the main focus of this analysis. We performed a statistical comparison of adverse findings observed in 116 short-term versus 78 long-term studies in order to explore the possibility of using only short-term studies as a prediction tool for the longer-term effects. Annotation of treatment related findings was one of the challenges faced during this work. A specific focus was therefore put on the summary and conclusion sections of the reports since they contain expert assessments on whether the findings were considered adverse or were attributed to other reasons. Our analysis showed a general good concordance between short-term and long-term toxicity findings for large molecules and the majority of small molecules. Less concordance was seen for certain “target organ systems findings’. While this work supports the minimization of in-vivo study durations, a larger-scale effort would be needed to provide more evidence. We therefore present the steps performed in this study as an open-source R workflow (CSL-Tox) and we provide the dataset used in the work to allow researchers to reproduce such analysis and to promote large-scale application of this study.
The Defenders of the Alveolus Succumb in COVID-19 Pneumonia to SARS-CoV-2, Necroptosis, Pyroptosis and Panoptosis
Authors: Schifanella Luca , Anderson Jodi , Wieking Garritt , Southern Peter J. , Antinori Spinello , Galli Massimo , Corbellino Mario , Lai Alessia , Klatt Nichole , Schacker Timothy W. , Haase Ashley T. 
Published: August 2022

SUMMARYThe alveolar type II (ATII) pneumocyte has been called the defender of the alveolus because, amongst the cell’s many important roles, repair of lung injury is particularly critical. We investigated the extent to which SARS-CoV-2 infection incapacitates the ATII reparative response in fatal COVID-19 pneumonia, and describe massive infection and destruction of ATI and ATII cells. We show that both type I interferon-negative infected ATII and type I-interferon-positive uninfected ATII cells succumb to TNF-induced necroptosis, BTK-induced pyroptosis and a new PANoptotic hybrid form of inflammatory cell death that combines apoptosis, necroptosis and pyroptosis in the same cell. We locate pathway components of these cell death pathways in a PANoptosomal latticework that mediates emptying and disruption of ATII cells and destruction of cells in blood vessels associated with microthrombi. Early antiviral treatment combined with inhibitors of TNF and BTK could preserve ATII cell populations to restore lung function and reduce hyperinflammation from necroptosis, pyroptosis and panoptosis.GraphicHighlightsIn fatal COVID-19 pneumonia, the initial destruction of Type II alveolar cells by SARS-CoV-2 infection is amplified by infection of the large numbers of spatially contiguous Type II cells supplied by the proliferative reparative response.Interferon-negative infected cells and interferon-positive uninfected cells succumb to inflammatory forms of cell death, TNF-induced necroptosis, BTK-induced pyroptosis, and PANoptosis.All of the cell death pathway components, including a recently identified NINJ1 component, are localized in a PANoptosome latticework that empties in distinctive patterns to generate morphologically distinguishable cell remnants.Early combination treatment with inhibitors of SARS-CoV-2 replication, TNF and BTK could reduce the losses of Type II cells and preserve a reparative response to regenerate functional alveoli.