bluuebunny/crossref_metadata_2025 huggingface dataset:
Early Complications in Prepectoral Breast Reconstructions with and without Acellular Dermal Matrix: A Preliminary Analysis of Outcomes
Authors: Plotsker Ethan L. , Graziano Francis D. , Rubenstein Robyn N. , Haglich Kathryn , Allen Robert J. , Coriddi Michelle R. , Dayan Joseph H. , Poulton Richard , McKernan Cayla , Mehrara Babak J. , Matros Evan , Disa Joseph J. , Nelson Jonas A.
Published: May 2023

BACKGROUND:

Prepectoral tissue expander (TE) placement for two-stage postmastectomy reconstruction is usually performed in conjunction with insertion of acellular dermal matrix (ADM). However, the effects of ADM use on TE loss or other early complications remain unknown. Therefore, the aim of this study was to compare early postoperative complications in patients who underwent prepectoral breast implant reconstruction with or without ADM use.

METHODS:

We performed a retrospective cohort study of all patients at our institution who underwent prepectoral breast reconstruction from January 2018 to June 2021. The primary outcome was TE loss within 90 days of surgery; secondary outcomes included other complications including infection, TE exposure, mastectomy skin flap necrosis requiring revision, and seroma.

RESULTS:

Data on 714 patients with 1,225 TEs (1,060 with ADM, 165 without) were analyzed. Baseline demographics did not differ by ADM use, though mastectomy breast tissue weight was higher in patients without ADM (750.3 g vs. 540.8 g, p < 0.001). Rates of TE loss were similar in reconstructions with (3.8 percent) ADM and without (6.7 percent; p = 0.09). We also did not find differences in the rates of secondary outcomes between cohorts.

CONCLUSIONS:

ADM use had no statistically significant effect on early complication rates among patients undergoing breast reconstruction with prepectoral TEs. Still, we were underpowered and data trended toward statistical significance, so larger studies are required in the future. Additional research and randomized studies should focus on larger cohorts and examine long-term complications such as capsular contracture and implant malposition.
Symmetrical breast surgery: balancing procedures versus prophylactic mastectomy and immediate reconstruction
Authors: Bitoiu Brendon , Grigor Emma , Hardy Jacob , Zeitouni Camille , Arnaout Angel , Zhang Jing
Published: May 2023

Background:

Various techniques for management of the contralateral breast exist in patients with unilateral breast cancer including contralateral prophylactic mastectomy with immediate breast reconstruction (PMIBR), or symmetrisation techniques including augmentation, reduction, or mastopexy. The purpose of this prospective cohort study was to evaluate and compare complications and patient-reported satisfaction of patients with contralateral PMIBR versus having symmetrisation procedures.

Methods:

A 7-year, single institution, prospectively maintained data base was reviewed. Patient-reported BREAST-Q were obtained at baseline, 3-months, and 12-months prospectively. Post-operative complications, oncologic outcomes and BREAST-Q scores were compared.

Results:

249 patients were included, 93 (37%) of which had contralateral PMIBR and 156 (63%) which had contralateral symmetrisation. The patients who underwent PMIBR were younger and had less co-morbidities compared to patients with symmetrisation. Rates of major and minor complications were similar apart from higher rates of minor wound dehiscence in the PMIBR group. When comparing mean change at 12 months follow up to pre-operative results, there was a significant decrease in the physical well-being of chest in the symmetrisation compared to PMIBR group (2.94 vs. -5.69, p=0.042). There were no significant differences in mean breast satisfaction, psychosocial well-being, and non-significant decreases in sexual well-being between groups.

Conclusion:

Patients with unilateral breast cancer who underwent immediate contralateral breast management, with either contralateral PMIBR or symmetrisation techniques, demonstrated similar profiles of major complications and good overall satisfaction except one physical well-being domain. Management of the contralateral breast with symmetrisation may provide similar outcomes compared to PMIBR, which often is considered not necessary in patients without specific indications.
“Robot-assisted Capsulectomy with Immediate Reimplantation in Breast Reconstruction”
Authors: Oh So Min , Han Woo Yeon , Eom Jin Sup , Kim Eun Key , Han Hyun Ho
Published: May 2023

Recent reports have introduced robotic breast surgery for immediate breast reconstruction with an implant. However, relevant reports of robot-assisted breast reconstruction including capsulectomy are limited. Although capsulectomy lowers risk of capsular contracture and thus contributes to better aesthetic outcomes, total capsulectomy may have complications such as injury to axillary structures or chest wall and overlying skin devascularization. To minimize the risk of injury, the authors used a robotic system employing Da-vinci SP for total capsulectomy, which has freely movable arms and clear magnified 3D vision. Furthermore, compared with conventional procedures, robotic surgery has the critical advantage of minimal incision and concealed scars, contributing to positive patient aesthetic outcomes. Thus, this study suggests that robot-assisted capsulectomy is technically feasible and reliably guarantees patient safety during breast reconstruction with immediate reimplantation.
Transconjunctival fat repositioning blepharoplasty: is excess fat herniation a prerequisite?
Authors: Chen Jianwu , Wu Yanhong , Wang Yuzhi , Zhang Bin , Tang Jianbing , Wang Zhongshan , Huang Wenhua , Cheng Biao
Published: May 2023

Background:

The fat repositioning technique has been widely used for the treatment of tear trough deformity, and there is a strong belief that excess fat herniation is a prerequisite for the procedure.

Objective:

The purpose of this study was to evaluate its effect in patients with minimal or no excess fat herniation.

Methods:

A total of 232 patients underwent the procedure and met the inclusion criteria. Of them, 198 were primary cases, and 34 had a history of fat removal for blepharoplasty. The amount of infraorbital fat was evaluated preoperatively by palpation. Release of the tear trough ligament and fat redistribution were sequentially performed as previously described. Surgical outcome was assessed based on Hirmand’s grading system and the FACE-Q scales.

Results:

Tear trough deformities were eliminated in more than 85% of cases. Aesthetic results were comparable between the primary and secondary surgery groups. The percentage of patients who complained of extremely or moderately severe tear trough deformities decreased from 86.3% preoperatively to 34.0% postoperatively. The scores of the lower eyelid FACE-Q decreased significantly (P<0.05). Patients were satisfied with their decision to undergo blepharoplasty (78.2±18.7). Undercorrection of the tear trough occurred in 30 patients. Other complications included 12 cases of transient conjunctiva bleeding, 2 cases of eyelid numbness, and 6 cases of dry eye. These resolved spontaneously.

Conclusion:

Fat repositioning is a feasible and effective technique for the treatment of tear trough deformities in patients with minimal or no excess orbital fat herniation provided that a fat pad is palpable.

Level of Evidence:

4
Early Detection of Gastric Intramucosal Adenocarcinoma on 68Ga-FAPI PET/CT
Authors: Liu Huipan , Xiang Feifan , Deng Jia , Li Kehong , Chen Yue
Published: May 2023

18F-FDG PET/CT may sometimes not be an ideal imaging method for gastric adenocarcinoma. Because of the unstable physiological uptake of 18F-FDG in the gastrointestinal tract and muscles, it may interfere with the detection of lesions. We present a case of gastric intramucosal adenocarcinoma detected by 68Ga-FAPI PET/CT in a patient with nasopharyngeal carcinoma.
Visualization of Intermetastatic Heterogeneity in Mixed Neuroendocrine Carcinoma–Acinar Adenocarcinoma of the Prostate by 68Ga-PSMA, 68Ga-FAPI, and 18F-FDG PET/CT
Authors: Cai Jiayu , Xu Weizhi , Meng Tinghua , Pang YiZhen , Chen Haojun
Published: May 2023

Mixed neuroendocrine carcinoma–acinar carcinoma is an uncommon histological type of neuroendocrine prostate cancer. It has been rarely reported in de novo prostate malignancies. In this case, we present 68Ga-PSMA (prostate-specific membrane antigen), 68Ga-FAPI, and 18F-FDG PET/CT findings in the de novo form of mixed large-cell neuroendocrine carcinoma–acinar adenocarcinoma of the prostate. Different levels of radiotracer uptake were observed in different metastatic sites on 68Ga-PSMA, 68Ga-FAPI, and 18F-FDG PET/CT. This case demonstrates that the multitracer PET/CT strategy may be used for the noninvasive detection of the intermetastatic heterogeneity in metastatic neuroendocrine prostate cancer.
Endoscopically Assisted LeFort I Osteotomy for Minimally Invasive Orthognathic Surgery: A Technical Note
Authors: Osorio Jose , Martinez David , López Juan P. , Gonzalez Luis V.
Published: May 2023

Minimally invasive surgery in orthognathic surgery has gained popularity in recent years. This is mainly due to the benefit to the patient of achieving a better postoperative period and a faster recovery. However, one of the main difficulties is the lack of direct vision, which is a concern for the surgeon. For this reason, this technical note aims to propose endoscopically assisted LeFort I osteotomy for MI orthognathic surgery.
Soft Tissue Chondroma of the Chin
Authors: Kim Su Ram , An Soyeon , Lee Jun Yong
Published: May 2023

Soft tissue chondromas are benign tumors, generally of the hands or feet, very rarely of the head and neck region. Repeated microtrauma may be as an initiating factor. The authors describe a case of a soft tissue chondroma of the chin in a 58-year-old male who had used a continuous positive airway pressure face mask for obstructive sleep apnea for 3 years. The patient presented with a hard mass on his chin for 1 year. Computed tomography imaging showed a heterogeneous enhancing mass, with calcification in the subcutaneous layer. Intraoperatively, the mass was beneath the mentalis muscle and abutted the mental nerve, without bone involvement. The diagnosis was a soft tissue chondroma. The patient recovered fully, without recurrence. The primary cause of soft tissue chondromas is unknown. The authors consider that continuous use of a continuous positive airway pressure face mask may play a role in the etiology.
Bihemispheric Right Anterior Cerebral Artery, Fenestrated Origin of the Left Pericallosal Artery, Fenestrated Basilar Artery, Double Right Posterior Cerebral Artery
Authors: Rusu Mugurel Constantin , Lazăr Mihai , Vrapciu Alexandra Diana
Published: May 2023

Anatomical variations of the cerebral vasculature are frequently encountered. The archived magnetic resonance angiogram of a 62-year-old male patient was studied anatomically on planar slices and 3-dimensional volume renderings. Numerous anatomical variants were found in that single case. In the vertebrobasilar system were found: the proximal basilar artery fenestration, with a unilateral origin from that fenestration of an anterior inferior cerebellar artery, and the unilateral origin of the superior cerebellar artery from the P1 segment of the main posterior cerebral artery (PCA). There were also unilateral variants of the right internal carotid artery (ICA): a subvariant of an accessory PCA leaving the ICA as a hyperplastic anterior choroidal artery and united to the main PCA by a short communicating branch, distinctive of the posterior communicating artery in that side (unilateral double PCA); a right bihemispheric anterior cerebral artery (ACA) but with complete agenesis of the contralateral A1 ACA segment; from the right ACA continued an anatomically normal ipsilateral A2 segment and a short transverse contralateral A2 that, in turn, sent off long pericallosal and callosomarginal arteries; and fenestrated origin of the left pericallosal artery. Therefore, an arterial variant in one of the main cerebral circulations could not exclude anatomical variants in the other cerebral circulatory beds.
Topical Anesthetic versus Lidocaine Mixture for Pain Relief During Keloid Treatment: A Prospective, Split Study
Authors: Park Tae Hwan
Published: May 2023

Background:

The most common typical symptoms of keloids can be pain and itchiness. Intralesional corticosteroid administration is generally the first-line conservative treatment. Minimizing pain during intralesional corticosteroid injections into keloids should be aimed, as the treatment is often painful. There has yet to be a report on which local anesthetic technique is superior in keloid treatment between topical anesthetic versus lidocaine mixture injection.

Methods:

This was a single-center prospective study. The study included 100 patients with painful multiple/multifocal keloids aged 18 to 85 years and was performed between May 2021 and December 2022. Among multiple keloid lesions in a single patient, we assigned the keloids pretreated with topical cream application versus local injection. Then, subjects received 40 mg of intralesional corticosteroid injections into the keloids with a 26G needle to treat keloids. Patients rated the pain intensity of each lesion pretreated with two different anesthetic techniques on an 11-point numeric rating scale. A separate direct question of “Which technique would you recommend if you had to be injected again?” was given.

Results:

One-hundred patients with painful multiple/multifocal keloids were included in the study. Data on pain intensity numeric rating scale (NRS) revealed that injection techniques relieved the pain statistically significantly more than topical creams. (P<0.001) 63% of the participants (n=63) preferred the injection technique, while 25% preferred topical anesthetics. In total, 12% of patients responded that there was no difference between the two techniques.

Conclusion:

When comparing with topical lidocaine/prilocaine (EMLA) cream, a 1:1 mixture of 1% lidocaine and epinephrine significantly alleviated pain during and after the corticosteroid injection.
Pediatric trauma surgery in Iraq and Afghanistan: Mortality, indicators, and most common operating room interventions from 2007 to 2016
Authors: Oh Andrew S. , Schauer Steven G. , Adelgais Kathleen , Fletcher John L. , Karrer Frederick M.
Published: May 2023

BACKGROUND

The wars in Afghanistan and Iraq produced thousands of pediatric casualties, using substantial military medical resources. We sought to describe characteristics of pediatric casualties who underwent operative intervention in Iraq and Afghanistan.

METHODS

This is a retrospective analysis of pediatric casualties treated by US Forces in the Department of Defense Trauma Registry with at least one operative intervention during their course. We report descriptive, inferential statistics, and multivariable modeling to assess associations for receiving an operative intervention and survival. We excluded casualties who died on arrival to the emergency department.

RESULTS

During the study period, there were a total of 3,439 children in the Department of Defense Trauma Registry, of which 3,388 met inclusion criteria. Of those, 2,538 (75%) required at least 1 operative intervention totaling 13,824 (median, 4; interquartile range, 2–7; range, 1–57). Compared with nonoperative casualties, operative casualties were older and male and had a higher proportion of explosive and firearm injuries, higher median composite injury severity scores, higher overall blood product administration, and longer intensive care hospitalizations. The most common operative procedures were related to abdominal, musculoskeletal, and neurosurgical trauma; burn management; and head and neck. When adjusting for confounders, older age (unit odds ratio, 1.04; 1.02–1.06), receiving a massive transfusion during their initial 24 hours (6.86, 4.43–10.62), explosive injuries (1.43, 1.17–1.81), firearm injuries (1.94, 1.47–2.55), and age-adjusted tachycardia (1.45, 1.20–1.75) were all associated with going to the operating room. Survival to discharge on initial hospitalization was higher in the operative cohort (95% vs. 82%, p < 0.001). When adjusting for confounders, operative intervention was associated with improved mortality (odds ratio, 7.43; 5.15–10.72).

CONCLUSION

Most children treated in US military/coalition treatment facilities required at least one operative intervention. Several preoperative descriptors were associated with casualties' likelihood of operative interventions. Operative management was associated with improved mortality.

LEVEL OF EVIDENCE

Prognostic and Epidemiological; Level III.
Work Fatigue in Phosphoric Acid Industry Workers: How Work shift and Sleep Quality Affect Them?
Authors: Syaiful Dayinta Annisa , Paskarini Indriati , Martiana Tri , Oktavera Angela Tesalonika
Published: May 2023

Introduction

Manpower is a firm asset and it plays a role in determining the quality and quantity of items produced. Labour-intensive activities require a lot of energy. Work fatigue is one of the repercussions experienced by the workforce. This study aims to investigate the relationship between work shifts and sleep quality and subjective work fatigue at the phosphoric acid industry.

Material and Method

This study was conducted on all 44 workers using a cross-sectional technique. The PSQI questionnaire and the Subjective Feelings of Fatigue questionnaire was conducted to obtain the data. Spearman correlation and contingency coefficient test were used to analyse the data.

Result

There are 47.7% employees experienced moderate work fatigue. There was a strong relationship between work shift (p=0.637) and sleep quality (p=0.619) with work fatigue.

Conclusion

Special inspection at 2-4 am should be conducted to monitor the employees.
Neuronal composition of processing modules in human V1: laminar density for neuronal and non-neuronal populations and a comparison with macaque
Authors: Garcia-Marin V , Kelly JG , Hawken MJ
Published: May 2023

The neuronal composition of homologous brain regions in different primates is important for understanding their processing capacities. Primary visual cortex (V1) has been widely studied in different members of the Catarrhines or Old-World monkeys. Neuronal density is considered to be central in defining the structure--function relationship. In human, there are large variations in the reported neuronal density from prior studies. We found the neuronal density in human V1 was 79,000 neurons/mm3, which is 35% of the neuronal density previously determined in macaque V1. Laminar density was proportionally similar between human and macaque. In V1, the ocular dominance column (ODC) contains the circuits for the emergence of orientation preference and spatial processing of a point image in many mammalian species. Analysis of the total neurons in an ODC and of the full number of neurons in macular vision (the central 15 degrees) indicate that humans have 1.28 times more neurons than macaques even though the density of neurons in macaque is 3 times the density in human V1. We propose that the number of neurons in a functional processing unit rather than the number of neurons under a mm2of cortex is more appropriate for cortical comparisons across species.
Single Cell RNA Sequencing Reveals Emergent Notochord-Derived Cell Subpopulations in the Postnatal Nucleus Pulposus
Authors: Zhang Chenghao , Zhong Leilei , Lau Yian Khai , Wu Meilun , Yao Lutian , Schaer Thomas P. , Mauck Robert L. , Malhotra Neil R. , Qin Ling , Smith Lachlan J.
Published: May 2023

Intervertebral disc degeneration is a leading cause of chronic low back pain. Cell-based strategies that seek to treat disc degeneration by regenerating the central nucleus pulposus hold significant promise, but key challenges remain. One of these is the inability of therapeutic cells to effectively mimic the performance of native nucleus pulposus cells, which are unique amongst skeletal cell types in that they arise from the embryonic notochord. In this study we use single cell RNA sequencing to demonstrate emergent heterogeneity amongst notochord-derived nucleus pulposus cells in the postnatal mouse disc. Specifically, we established the existence of early and late stage nucleus pulposus cells, corresponding to notochordal progenitor and mature cells, respectively. Late stage cells exhibited significantly higher expression levels of extracellular matrix genes including aggrecan, and collagens II and VI, along with elevated TGF-β and PI3K-Akt signaling. Additionally, we identified Cd9 as a novel surface marker of late stage nucleus pulposus cells, and demonstrated that these cells were localized to the nucleus pulposus periphery, increased in numbers with increasing postnatal age, and co-localized with emerging glycosaminoglycan-rich matrix. Finally, we used a goat model to show the Cd9+ nucleus pulposus cell numbers decrease with moderate severity disc degeneration, suggesting that these cells are associated with maintenance of the healthy nucleus pulposus extracellular matrix. Improved understanding of the developmental mechanisms underlying regulation of ECM deposition in the postnatal NP may inform improved regenerative strategies for disc degeneration and associated low back pain.
Network-based approach elucidates critical genes in BRCA subtypes and chemotherapy response in Triple Negative Breast Cancer
Authors: Agrawal Piyush , Jain Navami , Gopalan Vishaka , Timon Annan , Singh Arashdeep , Rajagopal Padma S , Hannenhalli Sridhar
Published: May 2023

Breast cancers exhibit substantial transcriptional heterogeneity, posing a significant challenge to the prediction of treatment response and prognostication of outcomes. Especially, translation of TNBC subtypes to the clinic remains a work in progress, in part because of a lack of clear transcriptional signatures distinguishing the subtypes. Our recent network-based approach, PathExt, demonstrates that global transcriptional changes in a disease context are likely mediated by a small number of key genes, and these mediators may better reflect functional or translationally relevant heterogeneity. We apply PathExt to 1059 BRCA tumors and 112 healthy control samples across 4 subtypes to identify frequent, key-mediator genes in each BRCA subtype. Compared to conventional differential expression analysis, PathExt-identified genes (1) exhibit greater concordance across tumors, revealing shared as well as BRCA subtype-specific biological processes, (2) better recapitulate BRCA-associated genes in multiple benchmarks, and (3) exhibit greater dependency scores in BRCA subtype-specific cancer cell lines. Single cell transcriptomes of BRCA subtype tumors reveal a subtype-specific distribution of PathExt-identified genes in multiple cell types from the tumor microenvironment. Application of PathExt to a TNBC chemotherapy response dataset identified TNBC subtype-specific key genes and biological processes associated with resistance. We described putative drugs that target top novel genes potentially mediating drug resistance. Overall, PathExt applied to breast cancer refines previous views of gene expression heterogeneity and identifies potential mediators of TNBC subtypes, including potential therapeutic targets.
Hydraulic retention time drives changes in energy production and the anodic microbiome of a microbial fuel cell (MFC)
Authors: Castellano-Hinojosa Antonio , Gallardo-Altamirano Manuel J. , Pozo Clementina , González-Martínez Alejandro , González-López Jesús
Published: May 2023

Abstract

The fish-canning industry generates large quantities of wastewater that typically contains high concentrations of organic matter and salts. However, little is known about the potential valorization of this type of industrial wastewater using the microbial fuel cell (MFC) technology operated in a continuous flow mode. This study investigated the impacts of three different hydraulic retention times (HRT) on the performance, energy production, and prokaryotic and eukaryotic anodic microbiome of an MFC inoculated with activated sludge from a seafood industry and fed with synthetic wastewater that mimics fish-canning effluents. Three consecutive HRTs were studied: 1 day (HRT1), 3 days (HRT3), and 6 days (HRT6) for 30 days, 21 days, and 21 days, respectively. Voltage, current density, and power density were significantly greater at HRT1 compared to HRT3 and HRT6, whereas no differences in coulombic efficiency (CE) were detected among HRTs. Decreases in the efficiency of removal of organic compounds and increases in the abundance of archaeal communities with increased HRT was related to limited energy production at greater HRT. The increased energy production at HRT1 was tightly linked to increased and decreased absolute abundances of bacterial and archaeal communities, respectively. Variations in the HRT significantly impacted the diversity and composition of the prokaryotic community with critical impacts on energy production. The proliferation of known and diverse electroactive microorganisms, such as those belonging to the generaGeobacter,Shewanella,Arcobacter, andClostridium, was related to increased energy production at HRT1. However, HRT3 and HRT6 enhanced the growth of archaeal methanogens (mainlyMethanosarcinasp.), which negatively impacted current production. The eukaryotic community showed less sensitivity to changes in HRT and no significant impact on current production. The carbon oxygen demand and organic matter removal % increased from approximately 20% at HRT1 to almost 60% at HRT6. This study shows there is a critical balance between the HRT and prokaryotic microorganisms contributing to organic removal rate and increases and decreases in energy production in an MFC treating wastewater from the fish-canning industry and operated in a continuous mode.
Pelvic irradiation induces behavioral and neuronal damage through gut dysbiosis in a rat model
Authors: Venkidesh B S , Narasimhamurthy Rekha Koravadi , Jnana Apoorva , Reghunathan Dinesh , Sharan Krishna , Chandraguthi Srinidhi Gururajarao , Murali Thokur Sreepathy , Mumbrekar Kamalesh Dattaram
Published: May 2023

Background

Pelvic radiotherapy is the endorsed course of treatment for pelvic malignancies, which frequently cover pelvic primary tumor lesions as well as non-cancerous lymphatic drainage sites in the pelvic area. As a result, pelvic irradiation may indiscriminately cause harm to healthy tissues and organs in the pelvic area in individuals undergoing treatment. Some studies suggest that gut microbial dysbiosis can be correlated with the incidence of radiation-induced toxicities in cancer patients. Since, the consequences were earlier thought to be solely due to the targeted or non-targeted effect of radiation, the role of gut microbiota in the non-targeted effects of radiation and the mechanistic role of the gut-brain axis in the pelvic irradiation scenario is not well explored. Hence, the current study was carried out to explore implication of gut dysbiosis in behavioral and neuronal changes induced by pelvic irradiation.

Materials and Methods

3-4-month-old Sprague Dawley rats were given a single dose of 6 Gy pelvic irradiation. Fecal samples of control and treated mice were collected at different timepoints to assess microbial abundance and diversity using 16S rRNA-based metagenomic sequencing. Behavioral analysis, histological analysis of intestine, brain and gene expression analysis of brain hippocampus was performed to ascertain the indirect impact of microbial dysbiosis on cognition.

Results

Following pelvic irradiation, significant microbial dysbiosis and behavioral alterations were observed with distinct changes in the microbial diversity and a significant decline in the locomotor effect and anxiety level at each time point following radiation. Histological analysis revealed a significant reduction in villus distortion as well as a significant decrease in neuronal cells, matured neurons, and an increase in reactive astrocytes, suggesting that pelvic irradiation promotes neuroinflammation. Gene expression analysis revealed a significant reduction in neural plasticity. Altogether, this study demonstrated that gut dysbiosis caused by pelvic irradiation alters behavior, intestinal morphology, integrity, and brain neuronal maturation, as well as lowers the levels of neural plasticity expression.

Conclusion

Current study provides evidence for the influence of gut dysbiosis on pelvic irradiation induced cognitive impairment in a rat model.
Unexpected Kif4a functions in adult regeneration encompass a dual role in neurons and in proliferative repair Schwann cells
Authors: Correia Patrícia D. , de Sousa Bárbara M. , Chato-Astrain Jesús , Faria Joana P. , Estrada Veronica , Relvas João B. , Müller Hans W. , Carriel Víctor , Bosse Frank , Vieira Sandra I.
Published: May 2023

Contrary to the adult central nervous system (CNS), the peripheral nervous system (PNS) has an intrinsic ability to regenerate that, among others, passes by expressing regeneration-associated genes such as kinesin family members. We here show that Kinesin family motor protein 4a (KIF4A), associated to neurodevelopmental disorders and thought for long to be only embryonically expressed, is highly abundant in axons and Schwann cells of adult rat CNS and rat and human PNS. Moreover,Kif4ais up-regulated in injured PNS neurons, being detected in their nuclei and regrowing axons, consistent with its functions as a chromokinesin and in the axonal transport of e.g. β1-integrin and L1CAM. Interestingly,Kif4ais also highly up-regulated in Schwann cells transdifferentiating into a proliferative repair phenotype at the injured distal nerve stumps. A role forKif4ain cultured Schwann cells proliferation was confirmed, withKif4amRNA expression being ∼6-fold higher in proliferating versus growth-arrested Schwann cells, andKif4aknockdown impairing Schwann cells’ proliferation. To our knowledge, this is the first description of KIF4A expression in adult nervous systems, up-regulation in neuroregeneration and pro-neuroregenerative roles, including promoting Schwann cells proliferation. KIF4A dual role in axonal regeneration, through neurons and glia, places as an attractive target for future neuroregeneration therapies.
Biodiversity responses to forest cover loss: taxonomy and metrics matter
Authors: de Araujo Martins Clarissa , Pays Olivier , Souza Franco L. , Renaud Pierre-Cyril , Valente-Neto Francisco , Silveira Mauricio , Ochoa-Quintero Jose , Provete Diogo B. , Santos Cyntia Cavalcante , Melo Isabel , Rodrigues Marciel Elio , Duleba Samuel , Nunes André Valle , Ceballos-Rivera Oriana DJ. , de Oliveira Roque Fabio
Published: May 2023

The actions required for biodiversity conservation depend on species responses to habitat loss, which may be either neutral, linear, or non-linear. Here, we tested how taxonomic, functional, and phylogenetic diversity of aquatic insects, dragonflies, frogs, and terrestrial mammals, as well as their species composition respond to forest cover loss. We hypothesized that taxonomic, functional, and phylogenetic diversity would respond nonlinearly (thresholds) to forest cover loss. Our findings do not support the current idea that a single threshold value of forest cover loss is applicable across tropical regions, or that some biodiversity facets are consistently more sensitive than others across different taxa. Species compositional responses to forest cover loss showed general patterns with thresholds between 30-50%. These results highlight the importance to consider multiple biodiversity facets when assessing the effects of forest cover loss on biological communities.
High prevalence of Bovine Tuberculosis reported in Cattle and Buffalo of Eastern Nepal
Authors: Upadhyaya Nabin , Shrestha Nisha , Dahal Roshan , Yadav Sanjay Kumar , Thakur Rashmi , Aryal Dinesh , Pokharel Sujeeta , Luitel Bibhu , Rajbhandari Rajesh , Balseiro Ana M , de la Fuente Jose , Gortazar Christian , Karmacharya Dibesh
Published: May 2023

Livestock farming, specifically of cattle and buffalo, is crucial to Nepal’s economy, with more than 66% of the population involved in agriculture and animal husbandry. Animal tuberculosis (TB) caused byMycobacterium bovisis a chronic disease that affects these animals and results in economic losses due to reduced milk and meat productivity, fertility and mortality.M. bovisalso infects humans, non-human primates, goats and other mammals, and can afflict both cattle and buffalo.

Our study is a part of routine surveillance of prevalent diseases, includingM. bovis, in cattle and buffalo. We collected blood samples (n=400, 100 samples from each district) from selected eastern districts of Nepal. We used a Rapid Bovine TB Test Kit to test these samples for presence ofM. bovis.

Of the 400 samples collected, 74 animals (18.75%) tested positive forM. bovis, with the majority of positive samples coming from cattle (n=71, 17.75%) and only three from buffalo (<1%). Among the screened breeds of cattle and buffalo, Holstein Friesian cattle (HF) (n=43, 58%), Jersey-cross cattle (JX) (n=20, 27%), Local buffalo (n=8, 10.8%) and Murra breed buffalo (n=3, 4.1%) were found to carryM. bovis. The majority (50%) of infected animals were between 3-6 years old. Morang (n= 24 positive in cattle; n=1 positive in buffalo) and Jhapa (n= 22 positive in cattle; n=2 positive in buffalo) had the highest prevalence ofM. bovis, while all the positive cases in Sunsari (n=19) and Udaypur (n=6) were in cattle.

The fact that over 18% of the samples tested positive forM. bovisis of great concern. It is critical to thoroughly test animal products from these livestock prior to human consumption. To prevent and mitigateM. bovis-related infections in Nepal, a more comprehensive screening strategy coupled with more effective animal husbandry practices needs to be adapted.
Perception of Speech Turn Dynamics is preserved in Congenitally Deaf children with Cochlear Implants
Authors: Hidalgo Céline , Zielinski Christelle , Chen Sophie , Roman Stéphane , Truy Eric , Schön Daniele
Published: May 2023

Perceptual and speech production abilities of children with cochlear implants (CI) are usually tested by word and sentence repetition or naming tests. However, in their daily life they show very heterogeneous language skills. Here, we describe a way of increasing the ecological validity of language assessment, promoting the use of close to real-life listening situations. The setup consists in watching the audio-visual conversation of two individuals. Children’s gaze-switches from one speaker to the other serve as a proxy of their prediction abilities. Moreover, to better understand the basis and the impact of anticipatory behaviour, we also measured children’s ability to understand the dialogue content, their speech perception and memory skills as well as their rhythmic skills. Importantly, we compared children with CI performances with those of an age-matched group of children with NH. While children with CI revealed poorer speech perception and verbal working memory abilities than NH children, there was no difference in gaze anticipatory behaviour. Interestingly, in children with CI only, we found a significant correlation between dialogue comprehension, perceptive skills and gaze anticipatory behaviour. Our results confirm and extend to a conversational context previous findings showing an absence of predictive deficits in children with CI. The current design seems an interesting avenue to provide an accurate and objective estimate of anticipatory language behaviour in a rather ecological conversational context also with young children.
Cynipid wasps systematically reprogram host metabolism and restructure cell walls in developing galls
Authors: Markel Kasey , Novak Vlastimil , Bowen Benjamin P. , Tian Yang , Chen Yi-Chun , Sirirungruang Sasilada , Zhou Andy , Louie Katherine B. , Northen Trent R. , Eudes Aymerick , Scheller Henrik V. , Shih Patrick M.
Published: May 2023

Many insects have evolved the ability to manipulate plant growth to generate extraordinary structures called galls in which insect larva can develop while being sheltered within and feeding on the plant. In particular, Cynipid (Hymenoptera: Cynipidae) wasps have evolved to form some of the most morphologically complex galls known and generate an astonishing array of gall shapes, colors, and sizes. However, the biochemical basis underlying these remarkable cellular and developmental transformations remains poorly understood. A key determinant in plant cellular development is the deposition of the cell wall to dictate the physical form and physiological function of newly developing cells, tissues, and organs. However, it is unclear to what degree cell walls are restructured to initiate and support the formation of new gall tissue. Here, we characterize the molecular alterations underlying gall development using a combination of metabolomic, histological, and biochemical techniques to elucidate how leaf cells are reprogrammed to form galls. Strikingly, gall development involves an exceptionally coordinated spatial deposition of lignin and xylan to formde novogall vasculature. Our results highlight how Cynipid wasps can radically change the metabolite profile and restructure the cell wall to enable the formation of galls, providing new insights into the mechanism of gall induction and the extent to which plants can be entirely reprogrammed to form novel structures and organs.
Small extracellular vesicles but not microvesicles fromOpisthorchis viverrinipromote cell proliferation in human cholangiocytes
Authors: Chaiyadet Sujittra , Sotillo Javier , Smout Michael , Cooper Martha , Doolan Denise L. , Waardenberg Ashley , Eichenberger Ramon M. , Field Matt , Brindley Paul J. , Laha Thewarach , Loukas Alex
Published: May 2023

Chronic infection withO. viverrinihas been linked to the development of cholangiocarcinoma (CCA), which is a major public health burden in the Lower Mekong River Basin countries, including Thailand, Lao PDR, Vietnam and Cambodia. Despite its importance, the exact mechanisms by whichO. viverrinipromotes CCA are largely unknown. In this study, we characterized different extracellular vesicle populations released byO. viverrini(OvEVs) using proteomic and transcriptomic analyses and investigated their potential role in host-parasite interactions. While 120kOvEVs promoted cell proliferation in H69 cells at different concentrations, 15kOvEVs did not produce any effect compared to controls. The proteomic analysis of both populations showed differences in their composition that could contribute to this differential effect. Furthermore, the miRNAs present in 120k EVs were analysed and their potential interactions with human host genes was explored by computational target prediction. Different pathways involved in inflammation, immune response and apoptosis were identified as potentially targeted by the miRNAs present in this population of EVs. This is the first study showing specific roles for different EV populations in the pathogenesis of a parasitic helminth, and more importantly, an important advance towards deciphering the mechanisms used in establishment of opisthorchiasis and liver fluke infection-associated malignancy.
A chemical genetic screen uncovers novel seed priming agents capable of persistent perturbation of anthocyanin regulation inArabidopsis thaliana
Authors: Hiiback Katrina M. , Campbell Malcolm M.
Published: May 2023

Priming is a general term for a phenomenon in which exposure to an early environmental stimulus results in a more rapid or vigorous response when the plant is exposed to subsequent challenges. Various types of priming have been described: ‘systemic acquired resistance’ against biotic stimuli, ‘epigenetic stress memory’ induced by repeated abiotic stimuli, and ‘seed priming’ treatments which apply water and additional adjuncts to seeds to improve crop performance. Using a high-throughput chemical genomic approach, thousands of small molecules were screened to identify compounds capable of ‘chemical priming’, asking if these could serve as artificial environments to persistently induce altered response to later abiotic challenges when applied as seed treatments. Attenuation of expected visual anthocyanin accumulation was chosen as a screening phenotype due to the visual nature of these pigments, as well as their biological roles in development and stress response. Several novel structural categories of molecules were identified that had the ability to reduce total anthocyanin accumulation in 7-18-day old seedlings induced by later low temperature challenge, persisting days after the removal of the compounds. Application variables were explored with thought to future use of the priming compounds as functional treatments: a dose-dependent relationship was established, additional effects on growth and development were documented to ensure minimal detrimental side effects on the treated plants, and the necessary temporal window of treatment was explored and reduced. Cross testing of the priming treatments identified by low temperature screening for ability to reduce anthocyanin induction by alternative exogenous and endogenous conditions showed consistent attenuative effect and revealed that the effect of priming on this metabolic phenotype was not specific to low temperature response. The presented research represents a proof-of-concept for the functional potential of seed priming with novel compounds, and highlights anthocyanin accumulation as a flexible component of plant stress response.
Chondroitin sulfate, dermatan sulfate, and hyaluronic acid differentially modify the biophysical properties of collagen-based hydrogels
Authors: Cortes-Medina Marcos , Bushman Andrew R. , Beshay Peter E. , Adorno Jonathan J. , Menyhert Miles M. , Hildebrand Riley M. , Agarwal Shashwat S. , Avendano Alex , Song Jonathan W.
Published: May 2023

Fibrillar collagens and glycosaminoglycans (GAGs) are structural biomolecules that are natively abundant to the extracellular matrix (ECM). Prior studies have quantified the effects of GAGs on the bulk mechanical properties of the ECM. However, there remains a lack of experimental studies on how GAGs alter other biophysical properties of the ECM, including ones that operate at the length scales of individual cells such as mass transport efficiency and matrix microstructure. Here we characterized and decoupled the effects of the GAG molecules chondroitin sulfate (CS) dermatan sulfate (DS) and hyaluronic acid (HA) on the stiffness (indentation modulus), transport (hydraulic permeability), and matrix microarchitecture (pore size and fiber radius) properties of collagen-based hydrogels. We complement these biophysical measurements of collagen hydrogels with turbidity assays to profile collagen aggregate formation. Here we show that CS, DS, and HA differentially regulate the biophysical properties of hydrogels due to their alterations to the kinetics of collagen self-assembly. In addition to providing information on how GAGs play significant roles in defining key physical properties of the ECM, this work shows new ways in which stiffness measurements, microscopy, microfluidics, and turbidity kinetics can be used complementary to reveal details of collagen self-assembly and structure.
Peroxisomal tail-anchored proteins do not reach peroxisomes via ER, instead mitochondria can be involved
Authors: Somborac Tamara , Bal Güleycan Lutfullahoglu , Fatima Kaneez , Vihinen Helena , Paatero Anja , Jokitalo Eija , Paavilainen Ville O , Konovalova Svetlana
Published: May 2023

Peroxisomes are membrane-enclosed organelles with important roles in fatty acid breakdown, glycolysis, and biosynthesis of sterols and ether lipids. Defects in peroxisome biogenesis result in severe neurological diseases, such as Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease, and myelopathies. However, many aspects of peroxisomal biogenesis are not well understood. Here we investigated delivery of tail-anchored (TA) proteins to peroxisomes in mammalian cells. Using glycosylation assays we showed that peroxisomal TA proteins do not enter ER in both WT and peroxisome-lacking cells. We observed that in cells lacking the essential peroxisome biogenesis factor, PEX19, peroxisomal TA proteins localize mainly to mitochondria. However, in PEX3 KO cells, which lack peroxisomes as well, the endogenous TA protein, ACBD5, does not target mitochondria, suggesting that PEX3 plays an important role in targeting of peroxisomal TA proteins to mitochondria. Finally, to investigate peroxisomal TA protein targeting in cells with fully functional peroxisomes we used a proximity biotinylation approach. We showed that while ER-targeted TA construct was exclusively inserted into the endoplasmic reticulum (ER), peroxisome-targeted TA construct was inserted to both peroxisomes and mitochondria. Thus, in contrast to previous studies, our data suggest that peroxisomal TA proteins do not insert to the ER prior to their delivery to peroxisomes. Instead, mitochondria can play a role in the targeting of TA proteins to peroxisomes.
Genetics of skeletal proportions in two different populations
Authors: Bartell Eric , Lin Kuang , Tsuo Kristin , Gan Wei , Vedantam Sailaja , Cole Joanne B. , Baronas John M , Yengo Loic , Marouli Eirini , Amariuta Tiffany , Chen Zhengming , Li Liming ,   GIANT consortium,   China Kadoorie Biobank Collaborative Group, Renthal Nora E , Jacobsen Christina M. , Salem Rany M , Walters Robin G , Hirschhorn Joel N
Published: May 2023

Human height can be divided into sitting height and leg length, reflecting growth of different parts of the skeleton whose relative proportions are captured by the ratio of sitting to total height (as sitting height ratio, SHR). Height is a highly heritable trait, and its genetic basis has been well-studied. However, the genetic determinants of skeletal proportion are much less well-characterized. Expanding substantially on past work, we performed a genome-wide association study (GWAS) of SHR in ∼450,000 individuals with European ancestry and ∼100,000 individuals with East Asian ancestry from the UK and China Kadoorie Biobanks. We identified 565 loci independently associated with SHR, including all genomic regions implicated in prior GWAS in these ancestries. While SHR loci largely overlap height-associated loci (P < 0.001), the fine-mapped SHR signals were often distinct from height. We additionally used fine-mapped signals to identify 36 credible sets with heterogeneous effects across ancestries. Lastly, we used SHR, sitting height, and leg length to identify genetic variation acting on specific body regions rather than on overall human height.