bluuebunny/crossref_metadata_2025 huggingface dataset:
Determining the component-based operative time learning curve for robotic-assisted radical prostatectomy
Authors: Ambinder David , Wang Shu , Siddiqui Mohummad Minhaj
Published: August 2022

Objectives

To determine the learning curve (LC) of total operative time and the discrete components of the robotic-assisted radical prostatectomy (RARP) for a recent robotic fellowship‐trained urologic surgeon.

Materials and methods

We performed a retrospective analysis of RARP procedures performed by a single new attending surgeon from August 2015 to April 2019. Patients' demographics and operative details were assessed. Total operative time was divided and prospectively recorded in 7 parts: (a) docking robot, (b) dissecting seminal vesicles (SVs) (c) dissecting endopelvic fascia (EPF), (d) incising bladder neck (BN), (e) completing the dissection, (f) lymph node dissection, and (g) urethrovesical anastomosis (UVA) and robot undocking. Cumulative sum analysis was used to ascertain the LC for total operative time and the 7 parts of the procedure.

Results

One hundred twenty consecutive RARPs were performed. The LC was overcome at 25 cases for total operative time, 13 cases for docking the robot, 33 cases for dissecting SVs, 31 cases for dissecting EPF, 46 cases for incising BN, 38 cases for prostate dissection, 25 cases for lymph node dissection, and 52 cases for UVA. Total operative time was decreased 22.8% (p < 0.0001) and time for robot docking, dissecting SVs, dissecting EPF, incising BN, completing prostate dissection, lymph node dissection, and UVA were decreased 16.7%, 30.5%, 29.5%, 36.2%, 37.3%, 32.2%, and 26.9%, respectively (all p < 0.05).

Conclusions

We observed a 25-case LC for a fellowship-trained urologist to achieve stable operative performance of RARP surgery. Procedural components demonstrated variable LCs including the UVA that required upward of 52 cases.
Role of multiparametric magnetic resonance imaging in the diagnosis and staging of urinary bladder cancer
Authors: Shalaby Essam A. , Mohamed Ahmed R. , Elkammash Tarek H. , Abouelkheir Rasha T. , Housseini Ahmed M.
Published: August 2022

Objectives

To assess the role of multiparametric magnetic resonance imaging (mp-MRI) in the diagnosis and staging of urinary bladder cancer (BC).

Materials and methods

Fifty patients diagnosed with bladder masses underwent mp-MRI study. The results of 3 image sets were analyzed and compared with the histopathological results as a reference standard: T2-weighted image (T2WI) plus dynamic contrast-enhanced (DCE), T2WI plus diffusion-weighted images (DWI), and mp-MRI, including T2WI plus DWI and DCE. The diagnostic accuracy of mp-MRI was evaluated using receiver operating characteristic curve analysis.

Results

The accuracy of T2WI plus DCE for detecting muscle invasion of BC was 79.5% with a fair agreement with histopathological examination (κ = 0.59); this percentage increased up to 88.6% using T2WI plus DWI, with good agreement with histopathological examination (κ = 0.74), whereas mp-MRI had the highest overall accuracy (95.4%) and excellent agreement with histopathological data (κ = 0.83). Multiparametric MRI can differentiate between low- and high-grade bladder tumors with a high sensitivity and specificity of 93.3% and 98.3%, respectively.

Conclusions

Multiparametric MRI is an acceptable method for the preoperative detection and accurate staging of BC, with reasonable accuracy in differentiating between low- and high-grade BC.
The Language of Implant-based Breast Reconstruction: Can We Do Better?
Authors: Prabhu Shamit S. , Llull Ramon , Katz Adam J.
Published: August 2022

The management of breast cancer has experienced tremendous changes in the last half-century. In today’s multimodal approach to breast cancer, patients have the prospect of achieving a sense of normalcy after mastectomy thanks to advancements in oncology and breast reconstruction. Although the oncologic management of breast cancer has evolved over multiple centuries, implant-based breast reconstruction (IBBR) has only been around since the 1960s. The last half century has seen the conception of multiple techniques, novel devices, and new possibilities in hopes of achieving outcomes that are similar to or even better than the patient’s premorbid state. However, with all these changes, a new problem has arisen—inconsistencies in the literature on how IBBR is described. In this article, we will discuss potential sources of confusion in the IBBR literature and lexicon, highlighting specific terms that may have multiple meanings or interpretations depending on perspective, context, and/or intent. As a first step toward clarifying what we perceive as a muddied landscape, we propose a naming convention for IBBR that centers around four important variables especially pertinent to IBBR—the type of mastectomy performed, the timing of reconstruction, the type of device that is placed, and the pocket location for device placement. We believe that adoption of a more standardized, consistent, and descriptive lexicon for IBBR will help provide clearer communication and easier comparisons in the literature so that we may continue to deliver the best outcomes for our patients.
Culturally Responsive Practices in Treatment of Substance Use Disorders
Authors: Fox LaVonne , Heitkamp Thomasine
Published: August 2022

This article highlights the limitations of culturally relevant care for Indigenous people in the prevention, treatment, and recovery of substance use disorders. It provides recommendations for consideration that expand the capacity for cultural humility. The “one-size-fits-all” approach to providing services, employed by most health and human service providers who are non-Indigenous, has failed. These limitations are often because of a lack of understanding of the larger historical and cultural context of Indigenous people. The authors emphasize the importance of health and human service providers' acquisition of the requisite knowledge about the impact of colonization and trauma that guides a trauma-informed approach to treatment.

Sixteen suggestions are provided to serve as a guide when serving Indigenous populations. They include expanding the body of literature on evidence-based practices to include the voice of Indigenous populations through the application of a Community-Based Participatory Action Research approach. Critical to achieving these outcomes is an expansion of the number of behavioral health providers who are Indigenous through the adoption of pedagogical practices that better serve the educational needs of this population. In addition, expanding the capacity of the preservice workforce to understand the impact of colonialization and cultural genocide is paramount. The goal is to prevent the perpetuation of negative attitudes and beliefs that result in addiction treatment providers becoming frustrated with the outcome and blaming the patient. These suggestions, based on the literature, will maximize positive outcomes and can be adapted by a broad spectrum of providers of substance use disorder services.
Do Social Support, Self-Efficacy, Emotional Quality of Life, and Sociodemographic Factors Associate With Substance Use?
Authors: Bayindir Cevik Ayfer , Uykucu Armutcuoglu Gamze , Öztabak Esra Meryem , Kasapoglu Elcin Sabahat
Published: August 2022

Substance use among university students is a common problem in the world. However, there are insufficient data on its prevalence among health school students. Similarly, there are very few studies about the use of substances by health students in Turkey. These studies have been mostly limited to the use of alcohol and tobacco. To the best of our knowledge, no previous studies have examined the substance use among students studying at health-related departments. This study investigated the pattern of substance abuse and its relationship with social support, self-efficacy, emotional quality of life, and sociodemographic factors in health profession students. Data of the cross-sectional and correlational study were collected via WhatsApp. Participants completed a student information form, the Substance Abuse Proclivity Scale, the Drug Abuse Screening Test, the Multidimensional Scale of Perceived Social Support, the SF-36 Emotional Quality of Life Index, and the Self-Efficacy for Protecting from Substance Abuse Scale. Of the participants, 63.6% (n = 823) had a high proclivity for substance abuse. Students most frequently used cigarettes and cannabis, one of the narcotic drugs. Substance abuse and proclivity increased as the emotional quality of life, social support, and self-efficacy decreased (p < .05). Substance abuse proclivity and drug use were higher in men, immigrants, smokers and alcohol users, those with a trauma history, and those separated from their family (p < .05). Health education reduces substance use (p < .05). It is required to make attempts to prevent and eliminate substance abuse in health profession students.
Enhanced recovery after surgery in patients undergoing laparoscopic common bile duct exploration: A retrospective study
Authors: Li Guowei , Zhang Junjie , Cai Jianfeng , Yu Zusheng , Xia Qunfeng , Ding Wei
Published: August 2022

Few reports have focused on the use of enhanced recovery after surgery (ERAS) in laparoscopic common bile duct exploration (LCBDE) to promote the postoperative recovery of patients with choledocholithiasis. Therefore, this study aimed to explore the advantages and safety of ERAS in patients who underwent LCBDE. From December 2016 to February 2020, 86 and 84 patients were retrospectively enrolled in the control and ERAS groups, respectively. The perioperative insulin resistance index, perioperative C-reactive protein level, time of postoperative analgesic use, time of postoperative first flatus, time of abdominal drainage tube removal, time of liver function recovery, and postoperative complications were analyzed between the two groups. The insulin resistance index (1, 3, and 5 days postoperatively) and C-reactive protein level (1, 3, 5, and 7 days postoperatively) in the ERAS group were significantly lower than those in the control group (all P < .05). In terms of the postoperative rehabilitation efficacy, the time of postoperative activity of the patient, time of postoperative first flatus, time of postoperative analgesic use, time of abdominal drainage tube removal, time of postoperative T-tube closing, and length of postoperative hospital stay in the ERAS group were significantly shorter than those in the control group (all P < .05). Additionally, the overall incidence of postoperative complications in the ERAS group had a decreasing trend when compared with that in the control group (P = .05). ERAS can reduce the postoperative stress response and postoperative complications of patients undergoing LCBDE, promote rehabilitation and shorten the length of postoperative hospital stay and therefore has good social and economic benefits.
Exploring the Relationship Between Attachment and Pathological Personality Trait Domains in an Outpatient Psychiatric Sample
Authors: Radetzki Phillip , Wrath Andrew J. , McWilliams Lachlan , Olson Trevor , Adams Stephen , De Souza Dawn , Lau Bienca , Adams G. Camelia
Published: August 2022

The current study investigates the relationship between insecure attachment and pathological personality trait domains in a sample of psychiatric outpatients. Participants (N = 150) completed measures for attachment and personality. Bivariate correlations and multiple regression analyses investigated the extent to which insecure attachment and personality pathology were associated. Insecure attachment positively correlated with overall personality pathology, with attachment anxiety having a stronger correlation than attachment avoidance. Distinct relationships emerged between attachment anxiety and negative affectivity and attachment avoidance and detachment. Insecure attachment and male sex predicted overall personality pathology, but only attachment anxiety predicted all five trait domains. Insecure attachment might be a risk factor for pathological personality traits. Assessing attachment in clinical contexts and offering attachment-based interventions could benefit interpersonal outcomes.
Mental Health Public Stigma in US Jewish Communities
Authors: Gearing Robin E. , Brewer Kathryne B. , Smith Limor , Carr L. Christian , Roe David
Published: August 2022

Stigma is a multifaceted barrier for individuals living with mental illness, contributing to negative stereotypes, prejudice, and discrimination, and is underinvestigated in minority ethnic groups. This study examines the stigma within the US Jewish communities, specifically the following: a) differences in public stigma dimensions based on mental illness (e.g., major depressive disorder, anxiety disorder, schizophrenia, or alcohol use disorder) and sex; and b) whether participant characteristics influence the public stigma. A community-based sample of 317 self-identified Jewish individuals participated in an experimental randomized vignette survey on stigma and help-seeking beliefs toward various mental illness. Findings indicate differences in stigma based on stigmatized individuals' sex and diagnosis as well as participants' demographics. Schizophrenia and alcohol use disorder were stigmatized similarly, with lower stigma for depression and the least stigma toward anxiety. Of interest, younger males have the most treatability and professional efficacy stigma, and tailored stigma-reducing interventions are recommended.
Brown Tumors Belong to the Spectrum of KRAS-driven Neoplasms
Authors: Turek Daniel , Haefliger Simon , Ameline Baptiste , Alborelli Ilaria , Calgua Byron , Hartmann Wolfgang , Harder Dorothee , Flanagan Adrienne M. , Amary Fernanda , Baumhoer Daniel
Published: August 2022

Brown tumors are rare and generally self-limiting mass lesions of bone occurring in the context of hyperparathyroidism. Although commonly regarded as endocrine-driven tumor-like lesions, we detected pathogenic hotspot KRAS mutations in 10/16 brown tumors (62%) with similar frequencies found in cases affecting the peripheral and axial skeleton. Pathogenic mutations in other driver genes of the RAS-MAPK pathway were not identified. Our findings suggest brown tumors to represent true neoplasms driven by the activation of the RAS-MAPK signaling pathway. The frequent regression of brown tumors after normalization of hyperparathyroidism points to a second hit mediated by endocrine stimulation to be required for tumor development. Our findings underline the pathogenic relation of brown tumors to nonossifying fibroma and giant cell granuloma of the jaws which both appear histologically similar to brown tumors and are also driven by RAS-MAPK signaling pathway activation.
DICER1-Altered Extraovarian Moderately Differentiated Sertoli-Leydig Cell Tumor: Report of a Rare Case
Authors: Lau Joseph C.C. , McCluggage W. Glenn , Yuen Liz Y.P. , Shing Matthew M.K. , Chan Godfrey C.F. , Yam Felix S.D. , Leung Michael W.Y. , Ng Wai-Fu , Liu Anthony P.Y.
Published: August 2022

We report an unusual case of a pelvic extraovarian moderately differentiated Sertoli-Leydig cell tumor arising in a 4-yr-old female. The tumor contained a DICER1 pathogenic variant which was absent in the germline ruling out DICER1 syndrome. In reporting this case, we discuss the differential diagnosis and possible histogenesis and review reported cases of extraovarian Sertoli-Leydig cell tumor.
Microscopic Sertoliform Sex Cord Proliferation Involving Pelvic Peritoneum: Report of a Case Associated With Endosalpingiosis
Authors: Talia Karen L. , Ratnayake Gayanie , McCluggage W. Glenn
Published: August 2022

Microscopic sex cord proliferations are an uncommon finding, most often associated with ovarian or uterine stromal, epithelial, or mixed epithelial and stromal neoplasms. Rarely they occur in conjunction with a non-neoplastic process such as endometriosis or adenomyosis, and occasionally in the absence of concurrent pathology in locations such as the fallopian tube. Most reports of this phenomenon document adult granulosa cell tumor-like morphology but more uncommonly the proliferations exhibit Sertoliform features. We report a case of a multifocal sex cord proliferation (inhibin and calretinin positive; BerEP4 and epithelial membrane antigen negative) with Sertoliform features occurring in the pelvic peritoneum and associated with endosalpingiosis, a previously unreported phenomenon. We discuss the differential diagnosis and speculate that this represents a non-neoplastic phenomenon.
Nasal Airway Function After Prophylactic Intranasal Surgery for Excessive Maxillary Superior Repositioning: A Retrospective Cohort Study Using the Nasal Obstruction Symptom Evaluation Scale
Authors: Özcan Elif M. , Can Serhat , Aydil Bariş , Varol Altan
Published: August 2022

Purpose:

The purpose of this study is to evaluate the degree of nasal airway function after simultaneous intranasal corrective surgery and bimaxillary surgery in patients with excessive superior maxillary repositioning.

Materials and Methods:

A retrospective cohort study was conducted on consecutive LeFort I superior repositioning patients who also underwent simultaneous intranasal surgery to prevent airway obstruction between 2015 and 2019. The Nasal Obstruction Symptom Evaluation (NOSE) scale was administered to all participants before the operation and after 1 year.

Results:

Fifteen patients (n=12 females; n=3 males) among 440 bimaxillary orthognathic surgery patients were enrolled with inclusion criteria of maxillary impaction between 8 and 12 mm. All subjects underwent at least LeFort I osteotomy, septoplasty, bilateral inferior turbinectomy, and bilateral sagittal split osteotomy. Two patients received custom-made total joint prosthesis. The primary outcome variable investigated was nasal function. The mean preop Nasal Obstruction Symptom Evaluation score was 24.33 and the mean postop score was 5.

Conclusions:

Intranasal procedures performed simultaneously with 8 mm or more maxillary impaction improves postoperative functional outcome in terms of nasal airway patency and breathing. Partial inferior turbinectomies and septoplasty should be performed consistently to avoid nasal obstruction if the impaction of upper jaw exceeds 8 mm.
Surgical Management of Perforated Peptic Ulcer: A Comparative Meta-analysis of Laparoscopic Versus Open Surgery
Authors: Salman Mohamed AbdAlla , Issa Mohamed , Salman Ahmed , Tourky Mohamed , Elewa Ahmed , Alrahawy Mahmoud , Shetty Neehar , Elsherbiney Mohammed , Elhaj Mujahid Gasemelseed Fadlallah , Shaaban Hossam El-Din
Published: August 2022

Background:

Despite the widescale success of proton pump inhibitors to reducing the incidence of peptic ulcer disease, perforated peptic ulcer (PPU) remains a significant cause of severe complications and death. The implementation of open or surgical repair of PPU should be guided by reliable guidelines which are based on current systematic evidence.

Objectives:

To assess the comparative efficacy and safety of laparoscopic and open repair of PPU.

Methods:

A systematic review and meta-analysis was conducted based on retrospective, prospective cohort studies, and randomized clinical trials. Duration of surgery and postoperative complications and death were collected from eligible studies, and the outcomes were pooled using mean differences (MD) or relative risks (RRs) for numerical and binary outcomes, respectively. The estimated variance was expressed as 95% confidence intervals (95% CIs).

Results:

Forty-five studies were included (8456 patients, 56.08% underwent open repair, 6 prospective studies, 7 randomized clinical trials, and 32 retrospective studies). Compared with open repair, laparoscopic surgeries were associated with longer operative times (MD=8.36, 95% CI, 0.49-16.22), shorter hospital stay (MD=−2.74, 95% CI, −3.70 to−1.79), a higher risk of suture leakage (RR=1.91, 95% CI, 1.04-3.49) and lower risks of mortality (RR=0.57, 95% CI, 0.47-0.70), septic shock (RR=0.69, 95% CI, 0.49-0.98), renal failure (RR=0.38, 95% CI, 0.18-0.79), and wound infection (RR=0.26, 95% CI, 0.19-0.37).

Conclusion:

Laparoscopic repair of PPU showed promising safety outcomes; however, future well-designed randomized studies are warranted to reduce the observed performance bias and possible selection bias in individual studies.
Burden of Colovesical Fistula and Changing Treatment Pathways: A Systematic Literature Review
Authors: Froiio Caterina , Bernardi Daniele , Asti Emanuele , Bonavina Giulia , Conti Andrea , Carmignani Luca , Bonavina Luigi
Published: August 2022

Purpose:

Colovesical fistula (CVF) is a rare complication of sigmoid diverticulitis causing significant morbidity and quality of life impairment. Aim of this study was to analyze contemporary literature data to appraise the current standard of care and changes of treatment algorithms over time.

Materials and Methods:

A systematic review of the literature on surgical management of CVF was conducted through PUBMED, EMBASE, and COCHRANE databases, according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guidelines.

Results:

Fourteen papers published between 2014 and 2020 and including 1061 patients were analyzed. One-stage colonic resection with primary anastomosis, with or without loop ileostomy, was the most common surgical procedure. A laparoscopic or robotic approach was attempted in 39.5% of patients, and conversion rate to open surgery was 7.8%. Clavien-Dindo grade ≥3 complication rate, 30-day mortality, and recurrence rate were 7.4%, 1.5%, and 0.5%, respectively.

Conclusions:

Minimally invasive sigmoidectomy with primary anastomosis is safe and should be the first-choice approach for CVF. Bladder repair is not necessary after a negative intraoperative leak test. A standardized perioperative care can improve clinical outcomes and reduce the length of hospital stay and the duration of Foley catheterization.
Tranexamic Acid in Pediatric Hemorrhagic Trauma
Authors: Borgman Matthew A. , Nishijima Daniel K.
Published: August 2022

There is strong evidence in adult literature that tranexamic acid (TXA) given within three hours from injury is associated with improved outcomes. The evidence for TXA use in injured children is limited to retrospective studies and one prospective observational trial. Two studies in combat settings and one prospective civilian US study have found association with improved mortality. These studies indicate the need for a randomized controlled trial to evaluate the efficacy of TXA in injured children and to clarify appropriate timing, dose and patient selection. Additional research is also necessary to evaluate trauma induced coagulopathy in children. Recent studies have identified three distinct fibrinolytic phenotypes following trauma (hyperfibrinolysis, physiologic fibrinolysis, and fibrinolytic shutdown) which can be identified with viscohemostatic assays (VHA). Whether VHA can appropriately identify children that may benefit or be harmed by TXA is also unknown.

Level of evidence

Level II
Dance-communicated distances support nectar foraging as a supply-driven system
Authors: Ohlinger Bradley D. , Schürch Roger , Silliman Mary R. , Steele Taylor N. , Couvillon Margaret J.
Published: August 2022

Much like human consumers, honeybees adjust their behaviours based on resources' supply and demand. For both, interactions occur in fluctuating conditions. Honeybees weigh the cost of flight against the benefit of nectar and pollen, which are nutritionally distinct resources that serve different purposes: bees collect nectar continuously to build large honey stores for overwintering, but they collect pollen intermittently to build modest stores for brood production periods. Therefore, nectar foraging can be considered a supply-driven process, whereas pollen foraging is demand-driven. Here we compared the foraging distances, communicated by waggle dances and serving as a proxy for cost, for nectar and pollen in three ecologically distinct landscapes in Virginia. We found that honeybees foraged for nectar at distances 14% further than for pollen across all three sites (n= 6224 dances,p< 0.001). Specific temporal dynamics reveal that monthly nectar foraging occurs at greater distances compared with pollen foraging 85% of the time. Our results strongly suggest that honeybee foraging cost dynamics are consistent with nectar supply-driven and pollen demand-driven processes.
Differential changes in life cycle-event phenology provide a window into regional population declines
Authors: Hanmer Hugh J. , Boersch-Supan Philipp H. , Robinson Robert A.
Published: August 2022

Climate change affects the phenology of annual life cycle events of organisms, such as reproduction and migration. Shifts in the timing of these events could have important population implications directly, or provide information about the mechanisms driving population trajectories, especially if they differ between life cycle event. We examine if such shifts occur in a declining migratory passerine bird (willow warbler,
Phylloscopus trochilus
), which exhibits latitudinally diverging population trajectories. We find evidence of phenological shifts in breeding initiation, breeding progression and moult that differ across geographic and spring temperature gradients. Moult initiation following warmer springs advances faster in the south than in the north, resulting in proportionally shorter breeding seasons, reflecting higher nest failure rates in the south and in warmer years. Tracking shifts in multiple life cycle events allowed us to identify points of failure in the breeding cycle in regions where the species has negative population trends, thereby demonstrating the utility of phenology analyses for illuminating mechanistic pathways underlying observed population trajectories.
Neural operator learning of heterogeneous mechanobiological insults contributing to aortic aneurysms
Authors: Goswami Somdatta , Li David S. , Rego Bruno V. , Latorre Marcos , Humphrey Jay D. , Karniadakis George Em
Published: August 2022

Thoracic aortic aneurysm (TAA) is a localized dilatation of the aorta that can lead to life-threatening dissection or rupture.In vivoassessments of TAA progression are largely limited to measurements of aneurysm size and growth rate. There is promise, however, that computational modelling of the evolving biomechanics of the aorta could predict future geometry and properties from initiating mechanobiological insults. We present an integrated framework to train a deep operator network (DeepONet)-based surrogate model to identify TAA contributing factors using synthetic finite-element-based datasets. For training, we employ a constrained mixture model of aortic growth and remodelling to generate maps of local aortic dilatation and distensibility for multiple TAA risk factors. We evaluate the performance of the surrogate model for insult distributions varying from fusiform (analytically defined) to complex (randomly generated). We propose two frameworks, one trained on sparse information and one on full-field greyscale images, to gain insight into a preferred neural operator-based approach. We show that this continuous learning approach can predict the patient-specific insult profile associated with any given dilatation and distensibility map with high accuracy, particularly when based on full-field images. Our findings demonstrate the feasibility of applying DeepONet to support transfer learning of patient-specific inputs to predict TAA progression.
The role of inter-regional mobility in forecasting SARS-CoV-2 transmission
Authors: Schoot Uiterkamp Martijn H. H. , Gösgens Martijn , Heesterbeek Hans , van der Hofstad Remco , Litvak Nelly
Published: August 2022

In this paper, we present a method to forecast the spread of SARS-CoV-2 across regions with a focus on the role of mobility. Mobility has previously been shown to play a significant role in the spread of the virus, particularly between regions. Here, we investigate under which epidemiological circumstances incorporating mobility into transmission models yields improvements in the accuracy of forecasting, where we take the situation in The Netherlands during and after the first wave of transmission in 2020 as a case study. We assess the quality of forecasting on the detailed level of municipalities, instead of on a nationwide level. To model transmissions, we use a simple mobility-enhanced SEIR compartmental model with subpopulations corresponding to the Dutch municipalities. We use commuter information to quantify mobility, and develop a method based on maximum likelihood estimation to determine the other relevant parameters. We show that taking inter-regional mobility into account generally leads to an improvement in forecast quality. However, at times when policies are in place that aim to reduce contacts or travel, this improvement is very small. By contrast, the improvement becomes larger when municipalities have a relatively large amount of incoming mobility compared with the number of inhabitants.
On the origin of shear-band network patterns in ductile shear zones
Authors: Roy Nandan , Roy Arnab , Saha Puspendu , Mandal Nibir
Published: August 2022

Ductile yielding of rocks and similar solids localize shear zones, which often show complex internal structures due to the networking of their secondary shear bands. Combining observations from naturally deformed rocks and numerical modelling, this study addresses the following crucial question: What dictates the internal shear bands to network during the evolution of an initially homogeneous ductile shear zone? Natural shear zones, observed in the Chotonagpur Granite Gneiss Complex of the Precambrian craton of Eastern India, show characteristic patterns of their internal shear band structures, classified broadly into three categories: type I (network of antithetic low-angle Riedel (R) and synthetic P-bands), type II (network of shear-parallel C and P/R bands) and type III (distributed shear domains containing isolated undeformed masses). Considering strain-softening rheology, our two-dimensional viscoplastic models reproduce these three types, allowing us to predict the condition of shear band growth with a specific network pattern as a function of the following parameters: normalized shear zone thickness, bulk shear rate and bulk viscosity. This study suggests that complex anastomosing shear-band structures can evolve under simple shear kinematics in the absence of any pure shear component.
A mathematical foundation to support bidirectional mappings between digital models: an application of multi-scale modelling in manufacturing
Authors: Qi Q. , Terkaj W. , Urgo M. , Jiang X. , Scott P. J.
Published: August 2022

With manufacturing going through the Industry 4.0 revolution, a vast amount of data and information exchange leads to an increase in complexity of digitized manufacturing systems. To tackle such complexity, one solution is to design and operate a digital twin model under different levels of abstraction, with different levels of detail, according to the available information and scope of the model. To support efficient, coherent and stable information flows between models with different levels of detail, a mathematical structure, called a delta lens, has been explored and developed to support rigorous bidirectional transitions between the models. To support different types of abstractions in manufacturing, a hybrid delta lens has been proposed and its formal representation is developed to support the generalization of its structure and properties. Benefits of the proposed hybrid delta lenses are demonstrated through an application to an industrial case to support the modelling of an automatic, high-throughput assembly line.
The antique genetic plight of the Mediterranean monk seal (
Monachus monachus
)
Authors: Salmona Jordi , Dayon Julia , Lecompte Emilie , Karamanlidis Alexandros A. , Aguilar Alex , Fernandez de Larrinoa Pablo , Pires Rosa , Mo Giulia , Panou Aliki , Agnesi Sabrina , Borrell Asunción , Danyer Erdem , Öztürk Bayram , Tonay Arda M. , Anestis Anastasios K. , González Luis M. , Dendrinos Panagiotis , Gaubert Philippe
Published: August 2022

Disentangling the impact of Late Quaternary climate change from human activities can have crucial implications on the conservation of endangered species. We investigated the population genetics and demography of the Mediterranean monk seal (
Monachus monachus
), one of the world's most endangered marine mammals, through an unprecedented dataset encompassing historical (extinct) and extant populations from the eastern North Atlantic to the entire Mediterranean Basin. We show that Cabo Blanco (Western Sahara/Mauritania), Madeira, Western Mediterranean (historical range) and Eastern Mediterranean regions segregate into four populations. This structure is probably the consequence of recent drift, combined with long-term isolation by distance (
R
2
= 0.7), resulting from prevailing short-distance (less than 500 km) and infrequent long-distance dispersal (less than 1500 km). All populations (Madeira especially), show high levels of inbreeding and low levels of genetic diversity, seemingly declining since historical time, but surprisingly not being impacted by the 1997 massive die-off in Cabo Blanco. Approximate Bayesian Computation analyses support scenarios combining local extinctions and a major effective population size decline in all populations during Antiquity. Our results suggest that the early densification of human populations around the Mediterranean Basin coupled with the development of seafaring techniques were the main drivers of the decline of Mediterranean monk seals.
Genetic variation underlies plastic responses to global change drivers in the purple sea urchin,
Strongylocentrotus purpuratus
Authors: Strader Marie E. , Wolak Matthew E. , Simon Olivia M. , Hofmann Gretchen E.
Published: August 2022

Phenotypic plasticity and adaptive evolution enable population persistence in response to global change. However, there are few experiments that test how these processes interact within and across generations, especially in marine species with broad distributions experiencing spatially and temporally variable temperature and
p
CO
2
. We employed a quantitative genetics experiment with the purple sea urchin,
Strongylocentrotus purpuratus
, to decompose family-level variation in transgenerational and developmental plastic responses to ecologically relevant temperature and
p
CO
2
. Adults were conditioned to controlled non-upwelling (high temperature, low
p
CO
2
) or upwelling (low temperature, high
p
CO
2
) conditions. Embryos were reared in either the same conditions as their parents or the crossed environment, and morphological aspects of larval body size were quantified. We find evidence of family-level phenotypic plasticity in response to different developmental environments. Among developmental environments, there was substantial additive genetic variance for one body size metric when larvae developed under upwelling conditions, although this differed based on parental environment. Furthermore, cross-environment correlations indicate significant variance for genotype-by-environment interactive effects. Therefore, genetic variation for plasticity is evident in early stages of
S. purpuratus
, emphasizing the importance of adaptive evolution and phenotypic plasticity in organismal responses to global change.
Chemical reprogramming ameliorates cellular hallmarks of aging and extends lifespan
Authors: Schoenfeldt Lucas , Paine Patrick T. , Kamaludeen M. Nibrasul H. , Phelps Grace B. , Mrabti Calida , Perez Kevin , Ocampo Alejandro
Published: August 2022

The dedifferentiation of somatic cells into a pluripotent state by cellular reprogramming coincides with a reversal of age-associated molecular hallmarks. Although transcription factor induced cellular reprogramming has been shown to ameliorate these aging phenotypes in human cells and extend health and lifespan in mice, translational applications of this approach are still limited. More recently, chemical reprogramming via small molecule cocktails have demonstrated a similar ability to induce pluripotency in vitro, however, its potential impact on aging is unknown. Here, we demonstrated that partial chemical reprogramming is able to improve key drivers of aging including genomic instability and epigenetic alterations in aged human cells. Moreover, we identified an optimized combination of two reprogramming molecules sufficient to induce the amelioration of additional aging phenotypes including cellular senescence and oxidative stress. Importantly, in vivo application of this two-chemical combination significantly extendedC. eleganslifespan. Together, these data demonstrate that improvement of key drivers of aging and lifespan extension is possible via chemical induced partial reprogramming, opening a path towards future translational applications.
Thinking outside the CaaX-box: an unusual reversible prenylation on ALDH9A1
Authors: Suazo Kiall F. , Schey Garrett L. , Auger Shelby A. , Li Ling , Distefano Mark
Published: August 2022

Protein lipidation is a post-translational modification that confers hydrophobicity on protein substrates to control their cellular localization, mediate protein trafficking, and regulate protein function. In particular, protein prenylation is a C-terminal modification on proteins bearing canonical prenylation motifs catalyzed by prenyltransferases. Such types of proteins have been of interest owing to their potential association with various diseases. Chemical proteomic approaches have been pursued over the last decade to define prenylated proteomes (prenylome) and probe their responses to perturbations in various cellular systems. Here, we describe the discovery of prenylation of a non-canonical prenylated protein, ALDH9A1, which lacks any apparent prenylation motif. This enzyme was initially identified through chemical proteomic profiling of prenylomes in various cell lines. Metabolic labeling with an isoprenoid probe using overexpressed ALDH9A1 reveals that this enzyme can be prenylated inside cells but does not respond to inhibition by prenyltransferase inhibitors. Site-directed mutagenesis of the key residues involved in ALDH9A1 activity indicate that the catalytic C288 bears the isoprenoid modification likely through an NAD+-dependent mechanism. Furthermore, the isoprenoid modification is also susceptible to hydrolysis, indicating a reversible modification. We hypothesize that this modification originates from endogenous farnesal or geranygeranial, the established degradation products of prenylated proteins and results in a thioester form that accumulates. This novel reversible prenoyl modification on ALDH9A1 expands the current paradigm on protein prenylation by illustrating a potentially new type of protein-lipid modification that may also serve as a novel mechanism for controlling enzyme function.
The two-component system YesMN promotes pneumococcal host-to-host transmission, and regulates genes involved in zinc homeostasis
Authors: Zafar M. Ammar , Costa-Terryl Alicia , Young Taylor M.
Published: August 2022

The ability to sense and respond rapidly to the dynamic environment of the upper respiratory tract (URT) makes Streptococcus pneumoniae (Spn) a highly successful human pathogen. Two-component systems (TCS) of Spn sense and respond to multiple signals it encounters allowing Spn to adapt and thrive in various host sites. Spn TCS have been implicated in their ability to promote pneumococcal colonization of the URT and virulence. As the disease state can be a dead-end for a pathogen, we considered whether TCS would contribute to pneumococcal transmission. Herein, we determined the role of YesMN, an understudied TCS of Spn, and observe that YesMN contributes towards pneumococcal shedding and transmission but is not essential for colonization. The YesMN regulon includes genes involved in zinc homeostasis and glycan metabolism, which are upregulated during reduced zinc availability in a YesMN dependent fashion. Thus, we identify the YesMN regulon and the molecular signals it senses that lead to the activation of genes involved in zinc homeostasis and glycan metabolism. Furthermore, in contract to Spn mono-infection, we demonstrate that YesMN is critical for high pneumococcal density in the URT during influenza A (IAV) coinfection. We attribute reduced colonization of the yesMN mutant due to increased association with and clearance by the mucus covering the URT epithelial surface. Thus, our results highlight the dynamic interactions that occur between Spn and IAV in the URT, and the role that TCS play in modulation of these interactions.
Paternal obesity alters the sperm epigenome and is associated with changes in the placental transcriptome and cellular composition
Authors: Pépin Anne-Sophie , Jazwiec Patrycja A. , Dumeaux Vanessa , Sloboda Deborah M. , Kimmins Sarah
Published: August 2022

Paternal obesity has been implicated in adult-onset metabolic disease in offspring. However, the molecular mechanisms driving these paternal effects and the developmental processes involved remain poorly understood. One underexplored possibility is the role of paternally driven gene expression in placenta function. To address this, we investigated paternal high-fat diet-induced obesity in relation to sperm epigenetic signatures, the placenta transcriptome and cellular composition. C57BL6/J males were fed either a control or high-fat diet for 10 weeks beginning at 6 weeks of age. Males were timed-mated with control-fed C57BL6/J females to generate pregnancies, followed by collection of sperm, and placentas at embryonic day (E)14.5. Chromatin immunoprecipitation targeting histone H3 lysine 4 tri-methylation (H3K4me3) followed by sequencing (ChIP-seq) was performed on sperm to define obesity-associated changes in enrichment. Paternal obesity corresponded with altered sperm H3K4me3 enrichment at imprinted genes, and at promoters of genes involved in metabolism and development. Notably, sperm altered H3K4me3 was localized at placental enhancers and genes implicated in placental development and function. Bulk RNA-sequencing on placentas detected paternal obesity-induced sex-specific changes in gene expression associated with hypoxic processes such as angiogenesis, nutrient transport and imprinted genes. Paternal obesity was also linked to placenta development; specifically, a deconvolution analysis revealed altered trophoblast cell lineage specification. These findings implicate paternal obesity-effects on placenta development and function as one mechanism underlying offspring metabolic disease.

Summary sentence

Paternal obesity impacts the sperm epigenome at genes implicated in placenta development and is associated with an altered placenta transcriptome and trophoblast cell lineage specification.
The reproductive status of the host determines the tolerance and resistance toMycobacterium marinuminfection inDrosophila melanogaster
Authors: Arch Marta , Vidal Maria , Fuentes Esther , Abat Anmaw Shite , Cardona Pere Joan
Published: August 2022

Both the sex and the reproductive status of the host have a major impact on the regulation of the immune response against infection. Due thatDrosophila melanogasterhas become a powerful model for study such interactions, we wanted to understand whether the sex or the reproductive status has an impact on the tolerance or resistance of the host to the in the model of systemicMycobacterium marinuminfection. We measured gene expression by RT-qPCR of immune genes,diptericinanddrosomycin, as well as host survival and the bacillary load at time of death. We also assessed the impact of metabolic (by expression ofupd3andimpl2) and hormonal (byecRexpression) regulation in the protection against infection. Data showed that resistance increased in actively mating males and females, and also in mated females while reducing the tolerance to infection. The data also suggest the Toll and IMD pathways determine tolerance and resistance, respectively, while basal levels ofecRfavors the stimulation of the IMD pathway. A time related role has been found forupd3expression, linked to the increase or decrease in the mycobacterial load at the beginning and at the end of the infection, respectively. Finally,impl2expression has been related to the increase of resistance only in non-actively mating males. The results obtained allows further interpretation of the results when assessing the differences between sexes and highlights the role of the reproductive status inD. melanogasterto face infections, since our data demonstrated their importance to determine resistance and tolerance againstM. marinuminfection.
Lithography-less, frugal and long-term diffusion-based static gradient generating microfluidic device for high-throughput drug testing
Authors: Bachal Ketaki , Yadav Shital , Gandhi Prasanna , Majumder Abhijit
Published: August 2022

Drug testing is a vital step in identification of the potential efficacy of any new/existing drug and/or combinations of drugs. The conventional methods of testing the efficacy of new drugs using multi-well plates are time consuming, prone to evaporation loss and manual error. Microfluidic devices with automated generation of concentration gradient provide a promising alternative. The implementation of such microfluidic devices is still limited owing to the additional expertise and facilities required to fabricate and run these devices. Conventional microfluidic devices also need pumps, tubings, valves, and other accessories, making them bulky and nonportable. To address these problems, we have developed a method for fabricating microfluidic structures using a nonconventional technique by exploiting the Saffman-Taylor instability in lifted Hele-Shaw cell. Multi-channel structure molds with varying dimensions were fabricated by shaping ceramic polymer slurry and retaining the shape. Further using the mold thus made, polydimethyl siloxane (PDMS) devices offering static, stable, diffusion-based gradient were casted using soft lithography. We have demonstrated with COMSOL simulation, as well as using Fluorescein isothiocyanate (FITC), a fluorescent dye, that the concentration gradient can be generated in this device, which remains stable for at least 5 days. Using this multichannel device, in vitro drug efficacy was validated with two drugs namely-Temozolomide (TMZ) and Curcumin, one FDA approved and one under research, on glioblastoma cells (U87MG). The resulting IC50 values were consistent with those reported in literature. We have also demonstrated the possibility of conducting molecular assays post-drug testing in the device by microtubule staining after curcumin treatment on cervical cancer cells (HeLa). In summary, we have demonstrated a i) user-friendly, ii) portable, static drug testing platform that iii) does not require further accessories and can create iv) a stable gradient for long duration. Such a device can reduce the time, manual errors, fabrication and running expenditure, and resources to a great extent in drug testing.

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