bluuebunny/crossref_metadata_2025 huggingface dataset:
An Evolving Landscape
Authors: Black Grant G. , Chen Yunchan , Qin Nancy , Wang Marcos Lu , Huang Hao , Otterburn David M.
Published: April 2024

Purpose

Loss of breast sensation after mastectomy has been well documented. Postoperative reinnervation of the breast is influenced by factors including reconstructive technique, patient comorbidities, and adjuvant treatment. However, little attention has been paid to the differences in sensation across regions of the breast and the impact of reconstructive method on these regional differences over time.

Methods

Patients undergoing nipple-sparing mastectomy with immediate autologous or alloplastic reconstruction were prospectively followed. Neurosensory testing was performed in 9 breast regions using a pressure-specified sensory device. Patients were stratified by reconstructive technique, and regional sensation was compared at different preoperative and postoperative time points using Student t tests.

Results

One hundred ninety-two patients were included; 106 underwent autologous reconstruction via neurotized deep inferior epigastric artery perforator flap, and 86 underwent 2-stage alloplastic reconstruction. Preoperative sensation thresholds did not differ between reconstructive cohorts in any region and averaged 18.1 g/mm2. In the first year after mastectomy, decreased sensation was most pronounced in the inner breast regions and at the nipple areolar complex (NAC) in both reconstructive cohorts. At 4 years postoperatively, sensation increased the most at the NAC in the alloplastic cohort (34.0 g/mm2 decrease) and at the outer lateral region in the autologous cohort (30.4 g/mm2 threshold decrease). The autologous cohort experienced improved sensation compared with the alloplastic cohort in 5 of 9 regions at 1 year postoperatively, and in 7 of 9 regions at 4 years postoperatively; notably, only sensation at the outer superior and outer medial regions did not differ significantly between cohorts at 4 years postoperatively.

Conclusions

Although patients undergoing breast reconstruction experience increased breast sensation over time, the return of sensation is influenced by type of reconstruction and anatomic region. Regions closer to and at the NAC experience the greatest loss of sensation after mastectomy, although the NAC itself undergoes the most sensation recovery of any breast region in those with alloplastic reconstruction.

Autologous reconstruction via a neurotized deep inferior epigastric artery perforator flap results in increased return of sensation compared with alloplastic reconstruction, particularly in the inferior and lateral quadrants of the breast.
Disparities in Breast Reconstruction
Authors: Eregha Nicole , Villalvazo Yadira , De La Cruz Carolyn
Published: April 2024

Background

Breast reconstruction methods vary based on factors such as medical history, breast size, and personal preferences. However, disparities in healthcare exist, and the role race plays in accessing to different reconstruction methods is unclear. This study aimed to investigate the influence of race and/or ethnicity on the type of breast reconstruction chosen.

Methods

This retrospective cohort study analyzed the University of Pittsburgh Medical Center Magee Women's Hospital database, including patients who underwent breast cancer surgery from 2011 to 2022. Multivariate analysis examined race, reconstruction, and reconstruction type (P < 0.05).

Results

The database included 13,260 women with breast cancer; of whom 1763 underwent breast reconstruction. We found that 91.8% of patients were White, 6.8% Black, and 1.24% were of other races (Asian, Chinese, Filipino, Vietnamese, unknown). Reconstruction types were 46.8% implant, 30.1% autologous, and 18.7% combined. Among Black patients, autologous 36.3%, implant 32.2%, and combined 26.4%. In White patients, autologous 29.5%, implant 48%, and combined 18.2%. Among other races, autologous 36.3%, implant 40.9%, and combined 22.7%. In patients who underwent breast reconstruction, 85.2% underwent unilateral and 14.7% of patients underwent bilateral. Among the patients who had bilateral reconstruction, 92.3% were White, 6.1% were Black, and 1.5% were of other ethnicities.

Conclusions

Our analysis revealed differences in breast reconstruction methods. Autologous reconstruction was more common among Black patients, and implant-based reconstruction was more common among Whites and other races. Further research is needed to understand the cause of these variations.
Malnutrition in Head and Neck Free Flap Reconstruction as a Predictor of Adverse Outcomes
Authors: Herzog Isabel , Panchal Disha , Sikder Sonali , Park John B. , Mendiratta Dhruv , Mansukhani Priya A. , Lee Edward S.
Published: April 2024

Introduction

Malnutrition is associated with increased mortality in patients with head and neck (H&N) cancer. Because albumin levels are used as a surrogate for nutritional status, the purpose of this study is to assess whether malnutrition is associated with adverse postoperative outcomes in H&N free flap reconstruction.

Materials and Methods

The 2006–2018 National Surgical Quality Improvement Program Database was queried for patients undergoing flap procedures of the H&N based on Current Procedure Terminology codes. Patients were included if they were operated on by an otolaryngologist or when the primary surgical site was H&N. Nutritional status was categorized as malnourished (preoperative albumin level <3.5 g/dL) or normal (preoperative albumin level ≥3.5 g/dL). Major complications included pulmonary complications, cardiac complications, deep vein thrombosis/pulmonary embolism, and sepsis/septic shock. Minor complications included surgical infection, urinary tract infection, bleeding, and dehiscence. Data were analyzed via univariate chi-square and multivariate regression analyses.

Results

Of the patients, 2532 (83.3%) had normal albumin and 506 (16.7%) had hypoalbuminemia. Patients with hypoalbuminemia were more likely to have smoking history (P = 0.008), pulmonary comorbidity (P < 0.001), renal comorbidity (P = 0.018), disseminated cancer (P < 0.001), steroid use (P < 0.001), recent weight loss (P < 0.001), bleeding disorder (P = 0.023), and preoperative transfusion (P < 0.001). After adjustment for preoperative variance, malnourished patients were more likely to experience death (P < 0.001), return to operating room (P < 0.001), free flap failure (P = 0.008), pulmonary complication (P < 0.001), deep vein thrombosis/pulmonary embolism (P = 0.019), wound disruption (P = 0.042), intraoperative transfusion (P < 0.001), minor complication (P < 0.001), major complication (P < 0.001), and extended length of stay (P < 0.001). Of the patients with normal albumin, 2.1% experienced flap failure compared with 6.3% of patients with hypoalbuminemia. It should be noted that malnourished patients were 3.370 times more likely to experience flap failure (95% confidence interval, 1.383–8.212; P = 0.008) and 3.975 times more likely to experience death (95% confidence interval, 1.700–9.626; P = 0.001) than those with normal albumin.

Conclusion

Malnutrition is associated with death, flap failure, minor complications, and other major complications following H&N free flap surgery, even after controlling for preoperative variance. Optimizing preoperative nutrition status before free flap procedures may ameliorate morbidity and mortality in H&N patients.
An Updated Analysis of Body Contouring Malpractice Cases
Authors: Reese Alyssa , Navarro Alejandro , Kozlowski Katherine , Singh Simran , Vu Giap , Neimanis Sara , Burke Mark , Morrison Clinton
Published: April 2024

Introduction

Body contouring procedures are commonly performed in the United States for patients seeking to sculpt specific areas of their bodies. The aim of this study was to provide an updated analysis of the factors that influence medical malpractice litigation surrounding body contouring surgery.

Methods

The following terms were used to search the Westlaw Campus Legal research Database for cases with earliest documentation after January 2013: (“contouring” OR “abdominoplasty” OR “liposuction” OR “tummy tuck” OR “body lift” OR “thigh lift” OR “arm lift” OR “brachioplasty” OR “thighplasty” OR “lipectomy” OR “panniculectomy”) AND “surgery” AND “medical malpractice.” Cases were only included if there was a complaint of medical malpractice subsequent to a body contouring procedure, and details of the cases were provided. Information was collected on the location of the lawsuit, the earliest year of available case documentation, patient demographics, procedure(s) performed, alleged injury, specialty involvement, and verdicts.

Results

A total of 32 cases were included in the study. Most of the patients involved in the cases were women (n = 30, 93.8%) and alive (n = 28, 87.5%). New York state had the most cases (n = 7, 21.9%). Abdominoplasty (56.3%), liposuction (53.1%), and buttock augmentations (15.6%) were the most common procedures. Plastic surgeons were involved in 93.8% (n = 30) of the cases, and anesthesia, emergency medicine, dermatology, and oncology were also involved. Claims of malpractice most often discussed negligent technique (71.9%) and poor postoperative management (62.5%). Common postoperative complications were infection/sepsis (40.6%), scarring (31.3%), and emotional distress/prolonged pain (31.3%). One available ruling was in favor of the plaintiff.

Conclusion

Although many of the cases in this analysis cited negligent technique, none were founded in their argument. Because involvement in these cases can place a burden on attending physicians, clear expectations of postoperative infections, scarring, and prolonged pain should be addressed during the informed consent process.
Comparative Analysis of Ventral Hernia Repair and Transverse Abdominis Release With and Without Panniculectomy
Authors: Amro Chris , Ryan Isabel A. , Elhage Sharbel A. , Messa Charles A. , Niu Ellen F. , McGraw J. Reed , Broach Robyn B. , Fischer John P.
Published: April 2024

Introduction

Amid rising obesity, concurrent ventral hernia repair and panniculectomy procedures are increasing. Long-term outcomes of transverse abdominis release (TAR) combined with panniculectomy remain understudied. This study compares clinical outcomes and quality of life (QoL) after TAR, with or without panniculectomy.

Methods

A single-center retrospective review from 2016 to 2022 evaluated patients undergoing TAR with and without panniculectomy. Propensity-scored matching was based on age, body mass index, ASA, and ventral hernia working group. Patients with parastomal hernias were excluded. Patient/operative characteristics, postoperative outcomes, and QoL were analyzed.

Results

Fifty subjects were identified (25 per group) with a median follow-up of 48.8 months (interquartile range, 43–69.7 months). The median age and body mass index were 57 years (47–64 years) and 31.8 kg/m2 (28–36 kg/m2), respectively. The average hernia defect size was 354.5 cm2 ± 188.5 cm2. There were no significant differences in hernia recurrence, emergency visits, readmissions, or reoperations between groups. However, ventral hernia repair with TAR and panniculectomy demonstrated a significant increase in delayed healing (44% vs 4%, P < 0.05) and seromas (24% vs 4%, P < 0.05). Postoperative QoL improved significantly in both groups (P < 0.005) across multiple domains, which continued throughout the 4-year follow-up period. There were no significant differences in QoL among ventral hernia working group, wound class, surgical site occurrences, or surgical site occurrences requiring intervention (P > 0.05). Patients with concurrent panniculectomy demonstrated a significantly greater percentage change in overall scores and appearance scores.

Conclusions

Ventral hernia repair with TAR and panniculectomy can be performed safely with low recurrence and complication rates at long-term follow-up. Despite increased short-term postoperative complications, patients have a significantly greater improvement in disease specific QoL.
Are We Speaking the Same “Language” Regarding Underrepresented Groups in Plastic Surgery and Increasing Diversity Within Our Field?
Authors: Douglas Nerone K.O. , Moroni Elizabeth A. , De La Cruz Carolyn , Egro Francesco M.
Published: April 2024

Background

Plastic Surgery is one of the fields that lags behind the rest when it comes to surgeons from backgrounds underrepresented in medicine (URiM). Extensive research has shown that diversity in health care not only fosters inclusivity but also saves lives. The study aim is to quantify how many integrated plastic surgery residency programs have outlined criteria defining diversity goals and/or groups of people they consider to be URiM.

Methods

All American Council for Graduate Medical Education-accredited integrated plastic surgery program Web sites were reviewed for diversity missions/statements and explicit mentions of the racial and ethnic groups. Web sites were deemed “up-to-date” if they were last updated within 6 months before the initial data collection period. The data collection period was from November 20 to 29, 2022.

Results

A total of 86 program were reviewed. Only 8 programs (9%) had clear URiM criteria listed on their Web sites, whereas 26 (30%) relied on institution/department-wide criteria, 1 (1%) listed that they were adhering to American Association of Medical Colleges definition of URiM, and 51 programs (60%) had no form of definition for what is considered URiM. When looking at the programs that have some form of criteria for URiM (n = 35 [40%]), all programs (100%) considered African American/Black, Native American/Alaskan Native, Hispanic/Latinx, and Pacific Islander/Native Hawaiian as groups URiM. Assessing the same subset of programs that have a form of criteria listed (n = 35 [40%]), 19 (58%) had listed other groups outside of race/ethnicity considered to be URiM for their program, and 14 (42%) programs did not. Fourteen programs (74%) considered LGBTQIA+ as a URiM group.

Conclusion and Significance

There still is a great deal of heterogeneity among residency programs when it comes to identifying which medical students are URiM. Numerous plastic surgery organizations have placed diversity and inclusive excellence at the forefront of their agendas; however, it is critical that residency programs also actively align their efforts in an equitable and intentional way. This study serves to encourage residency programs to evaluate their mission toward diversity, equity, and inclusion and to spark discussion toward creating a clearer URiM definition to be consistent among all programs.
Impact of Comorbidities on Sensory Return After Breast Reconstruction
Authors: Qin Nancy , Black Grant G. , Chen Yunchan , Wang Marcos Lu , Huang Hao , Otterburn David M.
Published: April 2024

Purpose

Breast anesthesia after mastectomy and reconstruction has been an ongoing concern with few improvements made in recent years. At present, there is a lack of studies evaluating the impact of comorbidities on sensation restoration. Identifying risk factors (RF) will be helpful with preoperative counseling.

Methods

This was a prospective study on patients who underwent mastectomy and immediate implant-based or neurotized deep inferior epigastric perforator (DIEP) flap-based reconstruction. Neurosensory testing was performed at predefined time points using a pressure specified device. Patients were stratified based on reconstruction type and comorbidities, including obesity (≥30 kg/m2), age (>55 years), hypertension, alcohol use, and smoking status. Sensory comparisons among the comorbidity groups were conducted using unpaired 2-sample t tests.

Results

A total of 239 patients were included in this study with 109 patients in the implant cohort and 131 patients in the DIEP cohort. One patient underwent bilateral reconstruction using both reconstructive modalities. Preoperatively, age older than 55 years was identified as an RF for reduced breast sensation in the implant cohort (difference in threshold, 10.7 g/mm2), whereas obesity was identified as an RF in the DIEP cohort (difference in threshold, 8 g/mm2). During the first 2 years postreconstruction, age older than 55 years and tobacco use history were found to be negatively correlated with breast sensation for both cohorts. With DIEP reconstruction specifically, obesity was identified as an additional RF during the early postoperative period. Of note, none of the comorbidities were found to be long-term RFs for reduced breast sensitivity. All breast sensation levels returned to comparable levels across all comorbidities by 4 years postreconstruction.

Conclusions

Currently, various comorbidities have been recognized as RFs for several postoperative complications including extended postoperative stay, necrosis, infection, and reoperation. However, our findings suggest that, although age, smoking history, and obesity showed transient associations with reduced breast sensation during the initial years postreconstruction, they play no role in the long-term potential of sensory nerve regeneration.
Proliferation Patterns of MCF-7 Breast Cancer Cells in Lipoaspirate Conditioned Media
Authors: Chen Yunchan , Arbuiso Sophia , Qin Nancy , Vernice Nicholas A. , Black Grant G. , Brown Kristy A. , Otterburn David
Published: April 2024

Introduction

Autologous fat grafting (AFG) is a common technique used to enhance aesthetic outcomes in postmastectomy breast reconstruction patients. Adipokines are hormones secreted by adipose tissue that play a critical role in regulating metabolic processes and the immune system. However, dysregulated adipokine secretion and signaling can contribute to the development and progression of cancer by promoting angiogenesis, altering the immune response, and inducing the epithelial mesenchymal transition. We aimed to assess how breast cancer cells behave in conditioned media derived from fat grafting lipoaspirates and gain a better understanding of the potential interactions that may occur within the tumor microenvironment.

Methods

Patients who were undergoing AFG as a part of breast reconstruction at NY-Presbyterian/Weill Cornell Medical Center between March 2021 and July 2023 were consented and enrolled in the study. This study was approved by the Weill Cornell Medicine Institutional Review Board (#20-10022850-14). Conditioned media is created using 20% of patient lipoaspirate secretome and 80% starving media. The growth of MCF-7, a human ER/PR+ breast cancer cell line, in conditioned media is assessed using CyQUANT.

Results

The breast cancer cells incubated in conditioned media displayed similar growth trends as those in complete media, which is enriched for cell growth (P > 0.05). MCF-7 cell behavior in conditioned media differed significantly from their proliferation patterns when serum starved in 100% starving media (P < 0.05).

Discussion

Our results suggest that there may be inherent factors within the lipoaspirate that may promote MCF-7 proliferation. One potential implication is that AFG used for breast reconstruction should be delayed until local-regional disease control has been established. In addition, based on the in vitro proliferation patterns of breast cancer cells in conditioned media, the safety profile of AFG may be enhanced if the procedure is performed after attaining negative margins and the completion breast cancer treatment.
Cold Ischemia Time and Delayed Graft Function in Kidney Transplantation: A Paired Kidney Analysis
Authors: Husain Syed Ali , Khanna Sohil , Yu Miko , Adler Joel T. , Cron David C. , King Kristen L. , Schold Jesse D. , Mohan Sumit
Published: April 2024

Background.

We aimed to understand the association between cold ischemia time (CIT) and delayed graft function (DGF) after kidney transplantation and the impact of organ pumping on that association.

Methods.

Retrospective cohort study using US registry data. We identified kidney pairs from the same donor where both kidneys were transplanted but had a CIT difference >0 and ≤20 h. We determined the frequency of concordant (both kidneys with/without DGF) or discordant (only 1 kidney DGF) DGF outcomes. Among discordant pairs, we computed unadjusted and adjusted relative risk of DGF associated with longer-CIT status, when then repeated this analysis restricted to pairs where only the longer-CIT kidney was pumped.

Results.

Among 25 831 kidney pairs included, 71% had concordant DGF outcomes, 16% had only the longer-CIT kidney with DGF, and 13% had only the shorter-CIT kidney with DGF. Among discordant pairs, longer-CIT status was associated with a higher risk of DGF in unadjusted and adjusted models. Among pairs where only the longer-CIT kidney was pumped, longer-CIT kidneys that were pumped had a lower risk of DGF than their contralateral shorter-CIT kidneys that were not pumped regardless of the size of the CIT difference.

Conclusions.

Most kidney pairs have concordant DGF outcomes regardless of CIT difference, but even small increases in CIT raise the risk of DGF. Organ pumping may mitigate and even overcome the adverse consequences of prolonged CIT on the risk of DGF, but prospective studies are needed to better understand this relationship.
Promoting safe and appropriate use of miltefosine to treat tegumentary leishmaniasis in Brazil: a best practice implementation project
Authors: Silva Sarah Nascimento , Ribeiro Laís Raquel , Borges dos Santos Kelli , Cota Gláucia
Published: April 2024

Introduction:

Miltefosine is a new drug that was recently approved for the treatment of tegumentary leishmaniasis (TL) by the Brazilian health system. It has a teratogenic potential and requires follow-up of patients undergoing treatment. Improving compliance with best practices is essential to ensure the safe and appropriate use of this drug.

Objective:

This project aimed to implement best practices for the safe and appropriate use of miltefosine in the treatment of TL in the state of Minas Gerais, Brazil.

Methods:

This project was guided by the JBI Evidence Implementation Framework. Five best practice criteria were established based on the best available evidence. A baseline audit was conducted to measure current practice against best practice. Barriers to best practice were then identified and a follow-up audit was conducted to evaluate changes after the implementation of improvement strategies. Two sites were analyzed: a leishmaniasis reference service in Belo Horizonte, the capital of Minas Gerais, and 28 regional offices.

Results:

The baseline audit evaluated data from 197 miltefosine requests distributed across 13 regional sites. All requests from the reference service were compliant (100%). This is in contrast to the 60% compliance rate at the regional offices. The improvement strategies included intensifying direct communication with the regional health professionals, which increased the average compliance rate to 79.5%, 6 months after the interventions were introduced.

Conclusion:

This best practice implementation project effectively increased the compliance rate for the audited procedures. Communication from the reference site with the regional health professionals successfully increased compliance with best practices and promoted the safe and appropriate use of miltefosine. These strategies should analyzed and applied to improve other programs.

Spanish abstract:

http://links.lww.com/IJEBH/A184
Broadly neutralizing antibodies against emerging delta-coronaviruses
Authors: Rexhepaj Megi , Park Young-Jun , Perruzza Lisa , Asarnow Daniel , McCallum Matthew , Culap Katja , Saliba Christian , Leoni Giada , Balmeli Alessio , Yoshiyama Courtney , Dickinson Miles S , Quispe Joel , Brown Jack T , Tortorici M. Alejandra , Sprouse Kaitlin R , Taylor Ashley L , Starr Tyler N , Corti Davide , Begnini Fabio , Veesler David
Published: April 2024

Porcine deltacoronavirus (PDCoV) spillovers were recently detected in children with acute undifferentiated febrile illness, underscoring recurrent zoonoses of divergent coronaviruses. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated human spike (S)-directed monoclonal antibodies from transgenic mice and found that two of them, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryo-electron microscopy structures of PD33 and PD41 in complex with the PDCoV receptor-binding domain and S ectodomain trimer provide a blueprint of the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs inhibit PDCoV by competitively interfering with host APN binding to the PDCoV receptor-binding loops, explaining the mechanism of viral neutralization. PD33 and PD41 are candidates for clinical advancement, which could be stockpiled to prepare for possible future PDCoV outbreaks.
Trauma Under Psychedelics: MDMA Shows Protective Effects During the Peritraumatic Period
Authors: Netzer Ophir , Magal Noa , Stern Yonatan , Polinsky Tzuk , Gross Raz , Admon Roee , Salomon Roy
Published: April 2024

Traumatic events (TEs) play a causal role in the etiology of psychopathologies such as depression and posttraumatic stress disorder (PTSD). Recent research has highlighted the therapeutic potential of psychoactive substances and especially 3,4-methylenedioxymethamphetamine (MDMA), in alleviating trauma symptoms in chronic patients. However, little is known regarding the consequences of trauma that is acutely experienced under the influence of psychoactive substances. Here we investigated the acute experiences and peritraumatic processing of 657 survivors from the high-casualty terror attack at the Supernova music festival in Israel on October 7th, 2023. Data were collected four to twelve weeks following the TE. Approximately two-thirds of survivors were under the influence of psychoactive substances at the time of the TE, offering a tragic and unique natural experiment on the impact of psychoactive compounds on TE processing. Our findings reveal that individuals who experienced the trauma while under the influence of MDMA demonstrated significantly improved intermediate outcomes compared to those who were under the influence of other substances or no substances at all. Specifically, the MDMA group reported increased feelings of social support, more social interactions and enhanced quality of sleep during the peritraumatic period, yielding reduced levels of mental distress and reduced PTSD symptom severity. These novel findings suggest that the influence of MDMA during the TE may carry protective effects into the peritraumatic period, possibly mediated through the known effects of MDMA in reducing negative emotions and elevating prosociality. These protective effects in turn may mitigate the development of early psychopathology-related symptoms. Current preliminary results underscore the need for further understanding of the cognitive and physiological processes by which psychedelic substances intersect with trauma recovery processes.
Deep learning modeling of rare noncoding genetic variants in human motor neurons definesCCDC146as a therapeutic target for ALS
Authors: Zhang Sai , Moll Tobias , Rubin-Sigler Jasper , Tu Sharon , Li Shuya , Yuan Enming , Liu Menghui , Butt Afreen , Harvey Calum , Gornall Sarah , Alhalthli Elham , Shaw Allan , Souza Cleide Dos Santos , Ferraiuolo Laura , Hornstein Eran , Shelkovnikova Tatyana , van Dijk Charlotte H. , Timpanaro Ilia S. , Kenna Kevin P. , Zeng Jianyang , Tsao Philip S. , Shaw Pamela J. , Ichida Justin K. , Cooper-Knock Johnathan , Snyder Michael P.
Published: April 2024

Amyotrophic lateral sclerosis (ALS) is a fatal and incurable neurodegenerative disease caused by the selective and progressive death of motor neurons (MNs). Understanding the genetic and molecular factors influencing ALS survival is crucial for disease management and therapeutics. In this study, we introduce a deep learning-powered genetic analysis framework to link rare noncoding genetic variants to ALS survival. Using data from human induced pluripotent stem cell (iPSC)-derived MNs, this method prioritizes functional noncoding variants using deep learning, links cis-regulatory elements (CREs) to target genes using epigenomics data, and integrates these data through gene-level burden tests to identify survival-modifying variants, CREs, and genes. We apply this approach to analyze 6,715 ALS genomes, and pinpoint four novel rare noncoding variants associated with survival, including chr7:76,009,472:C>T linked toCCDC146. CRISPR-Cas9 editing of this variant increasesCCDC146expression in iPSC-derived MNs and exacerbates ALS-specific phenotypes, including TDP-43 mislocalization. SuppressingCCDC146with an antisense oligonucleotide (ASO), showing no toxicity, completely rescues ALS-associated survival defects in neurons derived from sporadic ALS patients and from carriers of the ALS-associated G4C2-repeat expansion withinC9ORF72. ASO targeting ofCCDC146may be a broadly effective therapeutic approach for ALS. Our framework provides a generic and powerful approach for studying noncoding genetics of complex human diseases.
The subcommissural organ regulates brain development via secreted peptides
Authors: Zhang Tingting , Ai Daosheng , Wei Pingli , Xu Ying , Bi Zhanying , Ma Fengfei , Li Fengzhi , Chen Xing-jun , Zhang Zhaohuan , Zou Xiaoxiao , Guo Zongpei , Zhao Yue , Li Jun-Liszt , Ye Meng , Feng Ziyan , Zhang Xinshuang , Zheng Lijun , Yu Jie , Li Chunli , Tu Tianqi , Zeng Hongkui , Lei Jianfeng , Zhang Hongqi , Hong Tao , Zhang Li , Luo Benyan , Li Zhen , Xing Chao , Jia Chenxi , Li Lingjun , Sun Wenzhi , Ge Woo-ping
Published: April 2024

The subcommissural organ (SCO) is a gland located at the entrance of the aqueduct of Sylvius in the brain. It exists in species as distantly related as amphioxus and humans, but its function is largely unknown. To explore its function, we compared transcriptomes of SCO and non-SCO brain regions and found three genes,Sspo,Car3, andSpdef, that are highly expressed in the SCO. Mouse strains expressing Cre recombinase from endogenous promoter/enhancer elements of these genes were used to genetically ablate SCO cells during embryonic development, resulting in severe hydrocephalus and defects in neuronal migration and development of neuronal axons and dendrites. Unbiased peptidomic analysis revealed enrichment of three SCO-derived peptides, namely thymosin beta 4, thymosin beta 10, and NP24, and their reintroduction into SCO-ablated brain ventricles substantially rescued developmental defects. Together, these data identify a critical role for the SCO in brain development.
Generation and Characterization of Engineered Ubiquitin Variants to Modulate the Ubiquitin Signaling Cascade
Authors: Liang Chen T. , Roscow Olivia , Zhang Wei
Published: April 2024

The ubiquitin signaling cascade plays a crucial role in human cells. Consistent with this, malfunction of ubiquitination and deubiquitination is implicated in the initiation and progression of numerous human diseases, including cancer. Therefore, the development of potent and specific modulators of ubiquitin signal transduction has been at the forefront of drug development. In the past decade, a structure-based combinatorial protein-engineering approach has been used to generate ubiquitin variants (UbVs) as protein-based modulators of multiple components in the ubiquitin–proteasome system. Here, we review the design and generation of phage-displayed UbV libraries, including the processes of binder selection and library improvement. We also provide a comprehensive overview of the general in vitro and cellular methodologies involved in characterizing UbV binders. Finally, we describe two recent applications of UbVs for developing molecules with therapeutic potential.
Generation and Selection of Synthetic Human Antibody Libraries via Phage Display
Authors: Veggiani Gianluca , Sidhu Sachdev S.
Published: April 2024

Synthetic antibody libraries enable the development of antibodies that can recognize virtually any antigen, with affinity and specificity profiles that are superior to those of natural antibodies. By using highly stable and optimized frameworks, synthetic antibody libraries can be rapidly generated by precisely designing synthetic DNA, allowing absolute control over the position and chemical diversity introduced while expanding the sequence space for antigen recognition. Here, we describe a detailed protocol for the generation of highly diverse synthetic antibody phage display libraries based on a single framework, with diversity genetically incorporated by using finely designed mutagenic oligonucleotides. This general method enables the facile construction of large antibody libraries with precisely tunable features, resulting in the rapid development of recombinant antibodies for virtually any antigen.
Full counting statistics of charge in quenched quantum gases
Authors: Horváth Dávid X. , Rylands Colin
Published: April 2024

Unless constrained by symmetry, measurement of an observable on an ensemble of identical quantum systems returns a distribution of values which are encoded in the full counting statistics. While the mean value of this distribution is important for determining certain properties of a system, the full distribution can also exhibit universal behavior. In this paper we study the full counting statistics of particle number in one-dimensional interacting Bose and Fermi gases which have been quenched far from equilibrium. In particular, we consider the time evolution of the Lieb-Liniger and Gaudin-Yang models quenched from a Bose-Einstein condensate initial state and calculate the full counting statistics of the particle number within a subsystem. We show that the scaled cumulants of the charge in the initial state and at long times are simply related and, in particular, the latter are independent of the model parameters. Using the quasiparticle picture we obtain the full time evolution of the cumulants and find that although their end points are fixed, the finite-time dynamics depends strongly on the model parameters. We go on to construct the scaled cumulant generating functions and from this determine the limiting charge probability distributions at long time which are shown to exhibit distinct, nontrivial, and non-Gaussian fluctuations and large deviations.

Published by the American Physical Society
2024
Organizational justice, supervisor-provided resources and duty orientation: lessons from the mining sector
Authors: Ansong Abraham , Gnankob Robert Ipiin , Agyemang Isaac Opoku , Issau Kassimu , Okorley Edna Naa Amerley
Published: April 2024

Purpose

The study analysed the influence of organizational justice on the duty orientation of employees in the mining sector of Ghana. Also, it examined the mediating role of supervisor-provided resources in the relationship between organizational justice and duty orientation.

Design/methodology/approach

The study obtained data through a self-administered questionnaire from 291 employees of a mining firm. The data were analysed and interpreted in light of the hypotheses using the partial least squares structural equation modelling technique.

Findings

The findings revealed that organizational justice had a significant positive relationship with duty orientation and supervisor-provided resources. The results again established that supervisor-provided resources had a significant positive relationship with duty orientation. The study finally documented that supervisor-provided resources partially mediate the relationship between organizational justice and duty orientation.

Practical implications

We recommended that the management of the mining companies devote resources to developing organizational justice policies based on fairness in resource allocation, clear roles, employee feedback and effective information dissemination. Furthermore, supervisors should place priority on acquiring and dispensing resources as employees demonstrate their willingness to improve duty orientation.

Originality/value

The study contributes to knowledge in a novel research area. It adds to empirical evidence by highlighting the possible variables that may influence employees to engage in duty orientation.
Breaking barriers: paving the path to sustainable fashion – insights for a greener apparel and textile sector
Authors: Vishwakarma Amit , Mehrotra Deepti , Agrahari Ritu , Kharub Manjeet , Gupta Sumit , Jagtap Sandeep
Published: April 2024

Purpose

The apparel and textile sector poses a significant environmental challenge due to its substantial contribution to pollution in the form of air, water and soil pollution. To combat these issues, the adoption of sustainable practices is essential. This study aims to identify and analyse the barriers that hinder the progress of sustainability in the apparel and textile industry. By consulting experts in the field, critical barriers were identified and given special attention.

Design/methodology/approach

To achieve the research objective, an integrated approach involving Interpretive Structural Modelling (ISM) and fuzzy MICMAC decision-making techniques was employed. The results were further validated through the Decision-Making Trial and Evaluation Laboratory (DEMATEL) method.

Findings

The findings highlight that barrier related to clothing disposal, inadequate adaptation to modern technology, challenges affecting sector efficiency and issues related to fashion design are crucial in influencing the remaining six barriers. Based on the outcomes of the DEMATEL method, a comprehensive cause-and-effect diagram was constructed to gain a deeper understanding of these challenges.

Practical implications

This research provides valuable insights for policymakers and stakeholders in the apparel and textile industry. It offers a strategic framework to address and overcome sustainability barriers, promoting the development of a more environmentally responsible and resilient sector.

Originality/value

The purpose of this research is to conduct an in-depth investigation of the barriers apparel and textile sectors. It is feasible that both the management team and the medical experts who provide direct patient care could benefit from this research.
Impact of the COVID-19 pandemic on small and medium-sized enterprise (SME) government suppliers involved in government green procurement (GGP)
Authors: Masron Nurin Athilah , Zainol Zaini , Ismail Suhaiza
Published: April 2024

Purpose

The objectives of this paper are twofold. First, it aims to investigate the impact of the COVID-19 pandemic on the activities and performance of small and medium-sized enterprises (SMEs) government suppliers involved in government green procurement (GGP). Second, it examines the differences in the impact of COVID-19 between small and medium-sized groups.

Design/methodology/approach

The study used a questionnaire survey that was distributed to SMEs listed in the MyHIJAU directory that supply green goods and services to the government. Of the total 394 sample respondents, 126 usable questionnaires were received, representing a usable response rate of 31.98%. Descriptive analysis of mean score, standard deviation and mean score ranking was used to analyse the overall results. A t-test analysis was carried out to examine the differences between the small and medium-sized groups of companies.

Findings

The study discovers that the SME government suppliers involved in GGP were impacted by the COVID-19 pandemic. The top ranked impacts are that “the COVID-19 pandemic has heightened health and safety practices among the employees”, “the COVID-19 pandemic has reduced company’s turnover”, “the COVID-19 pandemic has forced the company to implement a cost reduction strategy”, “the COVID-19 pandemic has had a negative impact on the company’s ability to deliver work, supplies or services to the government” and “the COVID-19 pandemic has forced the company to incur higher production costs for green products or services provided”. However, there is no significant difference between the impact of the COVID-19 pandemic on the small and medium-sized group of enterprises.

Originality/value

The present study is among the fewer studies on the impact of the COVID-19 pandemic, with particular focus on SME government suppliers involved in GGP.
The impact of Industry 4.0 technologies on the resilience of established cross- border supply chains
Authors: Brookbanks Mike , Parry Glenn C.
Published: April 2024

Purpose

This study aims to examine the effect of Industry 4.0 technology on resilience in established cross-border supply chain(s) (SC).

Design/methodology/approach

A literature review provides insight into the resilience capabilities of cross-border SC. The research uses a case study of operational international SC: the producers, importers, logistics companies and UK Government (UKG) departments. Semi-structured interviews determine the resilience capabilities and approaches of participants within cross-border SC and how implementing an Industry 4.0 Internet of Things (IoT) and capitals Distributed Ledger (blockchain) based technology platform changes SC resilience capabilities and approaches.

Findings

A blockchain-based platform introduces common assured data, reducing data duplication. When combined with IoT technology, the platform improves end-to-end SC visibility and information sharing. Industry 4.0 technology builds collaboration, trust, improved agility, adaptability and integration. It enables common resilience capabilities and approaches that reduce the de-coupling between government agencies and participants of cross-border SC.

Research limitations/implications

The case study presents challenges specific to UKG’s customs border operations; research needs to be repeated in different contexts to confirm findings are generalisable.

Practical implications

Operational SC and UKG customs and excise departments must align their resilience strategies to gain full advantage of Industry 4.0 technologies.

Originality/value

Case study research shows how Industry 4.0 technology reduces the de-coupling between the SC and UKG, enhancing common resilience capabilities within established cross-border operations. Improved information sharing and SC visibility provided by IoT and blockchain technologies support the development of resilience in established cross-border SC and enhance interactions with UKG at the customs border.
The reporter's responsibility: Journalists and anthropologists
Authors: Laursen Eric
Published: April 2024

This guest editorial explores the parallel ethical responsibilities and institutional challenges faced by anthropologists and journalists, highlighting their shared commitment to reporting faithfully on the complexities of global conflicts, cultural transformations and sensitive social issues. It examines the pressures both professions encounter from institutional review boards and media sponsors, which can impede their ability to conduct in‐depth, culturally sensitive research and reporting. The text underscores the importance of honesty, expertise, open‐mindedness and courage in navigating the intricate cultural situations and conflicts within contemporary global issues. By examining the institutional pressures that demand conformity to specific ethical models or journalistic practices, the article calls for re‐evaluating these constraints to support reporters’ investigative integrity and ethical obligations better in both fields.
The bureaucratization of ethical integrity: Research ethics committees and imaginaries of risk
Authors: Shore Cris
Published: April 2024

This article critiques the expanding influence of research ethics committees (RECs) on social research, emphasizing their adverse effects on ethnographic methodologies. It argues that the bureaucratization of ethics, emphasizing compliance over contextual understanding, fundamentally misunderstands and impedes the nuanced nature of ethnographic work. Drawing on personal experiences and broader critiques, the article proposes the need for an alternative system that better accommodates the ethical complexities of social research, advocating for a more tailored approach that respects disciplinary methodologies and fosters genuine ethical engagement.
Fieldwork? Better not: Ethics bureaucracy in Eastern Europe
Authors: Budilová Lenka J. , Jakoubek Marek
Published: April 2024

This article discusses the methodological and ethical challenges posed by the bureaucratization of research ethics in Eastern Europe, particularly as this impacts the practice of anthropology and fieldwork. It reflects on the authors’ extensive fieldwork among Czech‐speaking Protestants in Bulgaria and the Czech Republic, highlighting the discrepancy between Western and Eastern European academic norms regarding ethnography. The authors argue that increased formalization and ethical regulation favour more easily bureaucratically managed methodologies, to the detriment of traditional anthropological fieldwork, which is critical for deep cultural understanding.
Far from neutral: Research ethics committees, interdisciplinarity and fieldwork
Authors: Halkias Alexandra
Published: April 2024

This article critiques research ethics committees (RECs) for stifling social sciences research through rigid, one‐size‐fits‐all ethics protocols. It highlights how these protocols, rooted in medical science perspectives, ignore the complexities of fieldwork, and prioritize institutional protection over knowledge advancement. The article illustrates the bureaucratic barriers to sociological and gender studies research through a case study involving fieldwork in a Greek hospital, showing how intersecting hierarchies in the field can render REC instruments invasive or moot. This article aims to enrich academic enquiry by acknowledging the diverse realities of research subjects and methodologies.
Claiming breathing space for anthropology: Ethnographic responsibility in changing times
Authors: Papataxiarchis Evthymios
Published: April 2024

This article explores the challenges of maintaining ethical ethnographic practices amid the evolving bureaucratic regulations of research ethics. Drawing on the author's fieldwork experiences in Lesvos, Greece, during different periods, including the recent European ‘refugee crisis’, it reflects on the deep ethics inherent in the ethnographic encounter, shaped by long‐term commitments and mutual exposure between the researcher and interlocutors. It critiques the bureaucratization of research ethics, arguing that legalistic guarantees, such as consent forms, undermine the nuanced, context‐dependent nature of ethnographic work. By contrasting engagements with locals, activists and professional humanitarians, the author highlights the tensions between bureaucratic regulation and the need for a flexible, situated approach to ethics, calling for a critical assessment of ethical frameworks to preserve the ‘breathing space’ essential for responsible and insightful ethnography. The article advocates for resistance against one‐size‐fits‐all ethical regulations constraining the rich potential of ethnographic research.