bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing Corruption
Authors: Brock Gillian
Published: June 2023

Chapter 4 canvasses some of the many mechanisms that are needed to address corruption effectively. Because there are multiple forms of corruption, controlling it requires diverse kinds of interventions and many agents will be involved in such interventions. As we come to appreciate, where the levels of corruption in a particular society are low, a vast array of mechanisms and agents are involved in controlling it. Chapter 4 includes coverage of at least ten important areas that require attention in our quest to address corruption. These include the importance of effective accountability mechanisms, appropriate transparency embedded in supportive contexts, and good institutional design. Promoting ethically robust processes, procedures, expectations, and strong institutions are also significant. Ensuring appropriate training is in place for employees so they can uphold corruption-curbing standards and professional conduct is similarly important, as is the need for robust procedures that can govern conflicts of interest. Independent oversight and monitoring will be crucial to sustained success of all interventions. When corruption involves a collective action problem, special attention is needed to reform social norms. Forming social action coalitions can be especially important in addressing several varieties of corruption. More generally, reducing corruption requires strong coalitions of stakeholders, including sector professionals, civil society organizations, and communities. The research survey also allows us to appreciate the many agents that have a role to play and therefore the range of actors that will potentially be in view as we move to the project of exploring agents’ responsibilities.
The Future of Deference in the World and Equivalence in the EU
Authors: Schürger Jonas
Published: June 2023

The fifth chapter turns away from the current legal system and attempts to give an outlook on the future global financial architecture. The first section of this chapter addresses the controversial question of how a truly global system should be designed. Is there a need for a harmonized and thus globally uniform supervisory law, or is competition between different national legal systems the better way for the future? This book aims at striking a balance between these positions. It is argued that the concept of deference should be an essential component of any future global financial market architecture. The second section of this chapter is devoted to the future of equivalence in the EU. European equivalence mechanisms should be refined and improved to overcome the challenges identified in the first two chapters. For this development, insights can be drawn from the experiences of deference in Switzerland and the US.
The importance of observing the client’s behaviour during psychological chat
Authors: Dewanti Septinda R , Astuti Budi
Published: June 2023

Nowadays, technology-based counselling like artificial intelligence (AI) and messenger-based counselling (MBC) is believed to be beneficial. However, how to observe and to interpret the client’s behaviour during MBC is not simple even for the counsellor, and AI will not be able to do so. For instance, the behaviours worth highlighting when conducting MBC are type-delete-retype-delete-retype, the typing period, emoticons and replay quickness.
Acute calcium pyrophosphate crystal arthritis is associated with an increased rate of hip and knee joint surgery
Authors: Harris David , Frampton Christopher , Patel Sandeep , White Douglas , Arad Uri
Published: June 2023

Objective

Acute calcium pyrophosphate (CPP) crystal arthritis is a distinct manifestation of calcium pyrophosphate crystal deposition (CPPD). No studies have specifically examined whether acute CPP crystal arthritis is associated with progressive structural joint damage. The objective of this retrospective cohort study was to evaluate the relative rate of hip and knee joint arthroplasties as an estimate of structural joint damage accrual, in a population of patients with acute CPP crystal arthritis.

Methods

Data were collected from Waikato District Health Board (WDHB) to identify an acute CPP crystal arthritis cohort with clinical episodes highly characteristic of acute CPP crystal arthritis. Data on hip and knee joint arthroplasties were collected from the New Zealand Orthopaedic Association’s Joint Registry. The rate of arthroplasties in the cohort was compared with the age–ethnicity-matched New Zealand population. Additional analysis was performed for age, obesity (BMI) and ethnicity.

Results

The acute CPP crystal arthritis cohort included 99 patients; 63 were male and the median age was 77 years (interquartile range, 71–82). The obesity rate was 36% with a median BMI of 28.4 kg/m2 (interquartile range, 25.8–32.2), comparable to the New Zealand population. The standardized surgical rate ratio in the cohort vs the age–ethnicity-matched New Zealand population was 2.54 (95% CI: 1.39, 4.27).

Conclusion

Our study identified a considerable increase in the rate of hip and knee joint arthroplasties in patients with episodes of acute CPP crystal arthritis. This suggests CPP crystal arthritis may be a chronic condition, leading to progressive joint damage.
Breaking Generational Curses: Success and Opportunity among Black Children of Incarcerated Parents
Authors: Gatewood Britany J , Muhammad Bahiyyah M , Turner Sydni
Published: June 2023

Black children are disproportionately represented among the children of incarcerated mothers and fathers in the United States. Research has largely focused on negative life outcomes (e.g., incarceration, negative behaviors, school dropout rates) of these children. Recently, studies have begun to look at success; however, children of incarcerated parents are typically placed into a homogenous group without considering racial implications. Using a critical race theoretical perspective, this study highlights the counternarrative of success by analyzing 59 in-depth interviews. Findings center on the ways adult Black children of incarcerated parents define success, which differs from middle-class, Eurocentric definitions of economic success, college graduation, marriage, and children as the success indicators. Success in relationships, community, education, and mental health emerged as the themes that define success. Findings show that their relationship with others (including their incarcerated parent), giving back to the community, educational experiences, and improving their mental health were indicators that they have “made it.” With support from their personal networks, they can succeed despite institutional and structural barriers. This study may assist policymakers, organizations, and schools with shifting societal perceptions to tailor resources for Black children of incarcerated parents to help invest in their futures.
Update on copper and selenium in Canadian cow–calf herds: regional differences and estimation of serum reference values
Authors: Waldner Cheryl , McLeod Lianne , Parker Sarah , Campbell John
Published: June 2023

Trace mineral supplementation of beef cattle is essential for efficient reproduction and herd health. Understanding regional differences in cow trace mineral status could inform decisions about risks of deficiencies and supplementation management. Cow–calf surveillance projects provided three opportunities to evaluate the trace mineral status of Canadian beef cow herds. Blood samples were collected at pregnancy testing in 2014 from 102 cow–calf herds and in 2016 from 86 cow–calf herds in Western Canada. In 2019, blood samples were collected at pregnancy testing from cows in 163 cow–calf herds from Eastern and Western Canada. Serum samples were analyzed for copper, selenium, and molybdenum concentrations using a plasma mass spectrometer. The prevalence of copper deficient cows sampled from the Western provinces ranged from 24% to 43% across the three periods, and was 20% from Eastern Canada in 2019. The prevalence of selenium deficient cows ranged from 0.2% to 0.4% across the three projects in Western Canada, but was higher in Eastern Canada at 4.6% in 2019. High serum molybdenum was identified in 9.4% to 14% of cows across the three periods in Western Canada and in 15% of cows sampled in Eastern Canada in 2019. Serum copper, selenium, and molybdenum concentrations varied by cow age and month of sample collection. Serum selenium and molybdenum concentrations, but not copper, varied by soil type associated with the location of the farm. A subsample of samples from cows from Western Canadian herds provided body condition score (BCS) data, pregnancy status, and calf survival data and were used to estimate updated serum reference values for adequate concentrations. Age-specific values were required for selenium and molybdenum. Reference intervals (80%) were estimated from 2,406 pregnant beef cows from 99 herds with each cow having a BCS ≥ 2.5/5 and a live calf at 3 wk with no retained placenta: copper for all cows (0.379 to 0.717 ppm), selenium for cows <4 yr (0.052 to 0.152 ppm), and selenium for cows ≥4 yr (0.064 to 0.184 ppm). Upper 90% reference limits were also estimated for serum molybdenum for cows <4 yr (>0.104 ppm) and cows ≥4 yr (>0.110 ppm). The lower limits for the reference intervals for adequate copper and selenium are below those previously reported; nevertheless, they represent a large sample that was specifically applicable to extensively managed beef animals in western Canada.
Histopathological Investigation of Varietal Responses to Cercospora beticola Infection Process on Sugar Beet Leaves
Authors: Rahman Bhuiyan Md Ziaur , Solanki Shyam , del Rio Mendoza Luis E. , Borowicz Pawel , Lakshman Dilip K. , Qi Aiming , Ameen Gazala , Khan Mohamed F. R.
Published: June 2023

Cercospora leaf spot (CLS) is the most destructive foliar disease in sugar beet (Beta vulgaris). It is caused by Cercospora beticola Sacc., a fungal pathogen that produces toxins and enzymes which affect membrane permeability and cause cell death during infection. In spite of its importance, little is known about the initial stages of leaf infection by C. beticola. Therefore, we investigated the progression of C. beticola on leaf tissues of susceptible and resistant sugar beet varieties at 12-h intervals during the first 5 days after inoculation using confocal microscopy. Inoculated leaf samples were collected and stored in DAB (3,3′-diaminobenzidine) solution until processed. Samples were stained with Alexa Fluor-488-WGA dye to visualize fungal structures. Fungal biomass accumulation, reactive oxygen species (ROS) production, and the area under the disease progress curve were evaluated and compared. ROS production was not detected on any variety before 36 h postinoculation (hpi). C. beticola biomass accumulation, percentage leaf cell death, and disease severity were all significantly greater in the susceptible variety compared with the resistant variety (P < 0.05). Conidia penetrated directly through stomata between 48 to 60 hpi and produced appressoria on stomatal guard cells at 60 to 72 hpi in susceptible and resistant varieties, respectively. Penetration of hyphae inside the parenchymatous tissues varied in accordance with time postinoculation and varietal genotypes. Overall, this study provides a detailed account to date of events leading to CLS disease development in two contrasting varieties.
Risk Factors of Infectious Complications in Pediatric Patients With Cerebral Palsy After Spinal Arthrodesis
Authors: Miskiewicz Michael , Hidalgo Perea Sofia , Magruder Matthew , Abdelgawad Amr
Published: June 2023

Study Design:

This was a retrospective study.

Objective:

The main objective of this study was to investigate (1) whether pediatric patients with cerebral palsy (CP) have higher rates of postoperative infectious complications after spinal fusion and (2) risk factors for postoperative infections.

Summary of Background Data:

Prior studies have shown that patients with CP undergo corrective spine surgery more often than the general population, yet typically have worse postoperative outcomes. Further investigation is needed to improve our understanding of the perioperative factors that place children with CP at greater risk of postoperative infectious complications.

Patients and Methods:

The 2019 “American College of Surgeons National Surgical Quality Improvement Program” Pediatric database was used for patient data. The univariable analysis compared the prevalence of preoperative comorbidities and perioperative factors between children with and without CP. Multivariable logistic regression modeling was used to ascertain independent risk factors for postoperative infectious complications.

Results:

A total of 4445 patients were included in the study; 606 (13.63%) patients had CP and 3839 (86.37%) did not. Patients with CP were more likely to have several notable preoperative comorbidities, and the rate of developing any infectious complication was more than 7 times greater in the CP cohort than in the control cohort (14.36% vs 1.88%; P<0.001). Multivariable analysis revealed CP [odds ratio (OR): 3.55, CI: 2.25–5.60; P<0.001], American Society of Anesthesiologists class 3 or higher (OR: 2.10, CI: 1.29–3.42; P = 0.003), and hematologic disorders (OR: 2.01, CI: 1.06–3.83; P = 0.033) to be independent risk factors for increased postoperative infectious complications.

Conclusions:

CP is an independent risk factor for the development of 30-day postoperative infectious complications in pediatric patients. In addition, the American Society of Anesthesiologists class 3 or higher and hematologic disorders were risk factors for postoperative infections after spinal fusion surgery.
Decreasing the Pedicle Screw Misplacement Rate in the Thoracic Spine With Robot-guided Navigation
Authors: Vardiman Arnold B. , Wallace David J. , Booher Grant A. , Toossi Nader , Bucklen Brandon S.
Published: June 2023

Study Design:

A retrospective chart review.

Objective:

The aim of this study was to evaluate the screw accuracy of thoracic pedicle screws placed with a robot-guided navigation system.

Summary of Background Data:

Thoracic pedicles are smaller in diameter than lumbar pedicles, making pedicle screw placement difficult. Misplaced pedicle screws may present complications including decreased construct stability, and increased risks of neurological deficits and blood vessel perforation. There is a dearth of knowledge on thoracic pedicle screw accuracy placed with a robot.

Materials and Methods:

A retrospective analysis of the robot-assisted placement of thoracic pedicle screws was performed. Preoperative and postoperative computed tomography (CT) scans of the implanted thoracic screws were collected to assess screw placement accuracy, pedicle breadth, and placement deviations. A CT-based Gertzbein and Robbins System was used to classify pedicle screw accuracy in 2 mm increments. A custom image overlay software was used to determine the deviations between the preoperatively planned trajectory of pedicle screws and final placement at screw entry (tail), and tip in addition to the angular deviation.

Results:

Seventy-five thoracic pedicle screws were implanted by navigated robotic guidance in 17 patients, only 1.3% (1/75) were repositioned intraoperatively. Average patient age and body mass index were 57.5 years and 25.9 kg/m2, respectively, with 52.9% female patients. Surgery diagnoses were degenerative disk disease (47.1%) and adjacent segment disease (17.6%). There were zero complications, with no returns to the operating room. According to the CT-based Gertzbein and Robbins pedicle screw breach classification system, 93.3% (70/75) screws were grade A or B, 6.6% (5/75) were grade C, and 0% were grade D or E. The average deviation from the preoperative plan to actual final placement was 1.8±1.3 mm for the screw tip, 1.6±0.9 mm for the tail, and 2.1±1.5 degrees of angulation.

Conclusions:

The current investigation found a 93.3% accuracy of pedicle screw placement in the thoracic spine. Navigated robot assistance is a useful system for placing screws in the smaller pedicles of the thoracic spine.

Level of Evidence:

Level III—retrospective nonexperimental study.
A Closed-system Technology for Mechanical Isolation of High Quantities of Stromal Vascular Fraction from Fat for Immediate Clinical Use
Authors: Solodeev Inna , Meilik Benjamin , Gur Eyal , Shani Nir
Published: June 2023

Background:

Adipose tissue stromal vascular fraction (SVF) is increasingly used in the clinic. SVF separation from fat by enzymatic disruption is currently the gold standard for SVF isolation. However, enzymatic SVF isolation is time-consuming (~1.5 h), costly and significantly increases the regulatory burden of SVF isolation. Mechanical fat disruption is rapid, cheaper, and less regulatory challenging. However, its reported efficacy is insufficient for clinical use. The current study evaluated the efficacy of a novel rotating blades (RBs) mechanical SVF isolation system.

Methods:

SVF cells were isolated from the same lipoaspirate sample (n = 30) by enzymatic isolation, massive shaking (wash), or engine-induced RBs mechanical isolation. SVF cells were counted, characterized by flow cytometry and by their ability to form adipose-derived stromal cells (ASCs).

Results:

The RBs mechanical approach yielded 2 × 105 SVF nucleated cells/mL fat, inferior to enzymatic isolation (4.17 × 105) but superior to cells isolating from fat by the “wash” technique (0.67 × 105). Importantly, RBs SVF isolation yield was similar to reported yields achieved via clinical-grade enzymatic SVF isolation. RBs-isolated SVF cells were found to contain 22.7% CD45-CD31−CD34+ stem cell progenitor cells (n = 5) yielding quantities of multipotent ASCs similar to enzymatic controls.

Conclusions:

The RBs isolation technology provided for rapid (<15 min) isolation of high-quality SVF cells in quantities similar to those obtained by enzymatic digestion. Based on the RBs platform, a closed-system medical device for SVF extraction in a rapid, simple, safe, sterile, reproducible, and cost-effective manner was designed.
2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension
Authors: Mancia Giuseppe , Kreutz Reinhold , Brunström Mattias , Burnier Michel , Grassi Guido , Januszewicz Andrzej , Muiesan Maria Lorenza , Tsioufis Konstantinos , Agabiti-Rosei Enrico , Algharably Engi Abd Elhady , Azizi Michel , Benetos Athanase , Borghi Claudio , Hitij Jana Brguljan , Cifkova Renata , Coca Antonio , Cornelissen Veronique , Cruickshank J. Kennedy , Cunha Pedro G. , Danser A.H. Jan , Pinho Rosa Maria de , Delles Christian , Dominiczak Anna F. , Dorobantu Maria , Doumas Michalis , Fernández-Alfonso María S. , Halimi Jean-Michel , Járai Zoltán , Jelaković Bojan , Jordan Jens , Kuznetsova Tatiana , Laurent Stephane , Lovic Dragan , Lurbe Empar , Mahfoud Felix , Manolis Athanasios , Miglinas Marius , Narkiewicz Krzystof , Niiranen Teemu , Palatini Paolo , Parati Gianfranco , Pathak Atul , Persu Alexandre , Polonia Jorge , Redon Josep , Sarafidis Pantelis , Schmieder Roland , Spronck Bart , Stabouli Stella , Stergiou George , Taddei Stefano , Thomopoulos Costas , Tomaszewski Maciej , Van de Borne Philippe , Wanner Christoph , Weber Thomas , Williams Bryan , Zhang Zhen-Yu , Kjeldsen Sverre E.
Published: June 2023

Document Reviewers:

Luis Alcocer (Mexico), Christina Antza (Greece), Mustafa Arici (Turkey), Eduardo Barbosa (Brazil), Adel Berbari (Lebanon), Luís Bronze (Portugal), John Chalmers (Australia), Tine De Backer (Belgium), Alejandro de la Sierra (Spain), Kyriakos Dimitriadis (Greece), Dorota Drozdz (Poland), Béatrice Duly-Bouhanick (France), Brent M. Egan (USA), Serap Erdine (Turkey), Claudio Ferri (Italy), Slavomira Filipova (Slovak Republic), Anthony Heagerty (UK), Michael Hecht Olsen (Denmark), Dagmara Hering (Poland), Sang Hyun Ihm (South Korea), Uday Jadhav (India), Manolis Kallistratos (Greece), Kazuomi Kario (Japan), Vasilios Kotsis (Greece), Adi Leiba (Israel), Patricio López-Jaramillo (Colombia), Hans-Peter Marti (Norway), Terry McCormack (UK), Paolo Mulatero (Italy), Dike B. Ojji (Nigeria), Sungha Park (South Korea), Priit Pauklin (Estonia), Sabine Perl (Austria), Arman Postadzhian (Bulgaria), Aleksander Prejbisz (Poland), Venkata Ram (India), Ramiro Sanchez (Argentina), Markus Schlaich (Australia), Alta Schutte (Australia), Cristina Sierra (Spain), Sekib Sokolovic (Bosnia and Herzegovina), Jonas Spaak (Sweden), Dimitrios Terentes-Printzios (Greece), Bruno Trimarco (Italy), Thomas Unger (The Netherlands), Bert-Jan van den Born (The Netherlands), Anna Vachulova (Slovak Republic), Agostino Virdis (Italy), Jiguang Wang (China), Ulrich Wenzel (Germany), Paul Whelton (USA), Jiri Widimsky (Czech Republic), Jacek Wolf (Poland), Grégoire Wuerzner (Switzerland), Eugene Yang (USA), Yuqing Zhang (China).
Can velmanase alfa be the next widespread potential therapy for alpha mannosidosis?
Authors: Abdul Ghani Sundus , Burney Sheeba , ul Hussain Hassan , Abdul Wahid Maryam , Mumtaz Hassan
Published: June 2023

Alpha-mannosidosis (AM) is an autosomal recessive lysosomal storage disorder caused by reduced activity of the enzyme alpha-mannosidase. The disease is characterized by immunodeficiency, facial and skeletal abnormalities, impaired hearing, and intellectual disability. The clinical subtype of AM shows considerable variability in an individual, and at present, at least three clinical subtypes are suggested. Diagnosis is made by identification of deficiency of α-mannosidase activity in nucleated cells, like fibroblasts. The children are often born apparently normal as the disease is insidiously progressive, hence making early diagnosis essential. Along with supportive care, long-term therapeutic options include hematopoietic stem cell transplant (HSCT), bone marrow transplantation (BMT) and enzyme replacement therapy (ERT). The possible benefits of these procedures must be weighed against the overall risk of procedure-related morbidity and mortality. Velmanase alfa is the first human recombinant form of alpha-mannosidase licensed and available for long-term ERT. It is approved for treating non-neurologic manifestations of mild to moderate AM. The results obtained from different clinical trials provide evidence of the positive clinical effect of the recombinant enzyme on patients with AM. Different routes of diagnosis and unspecific initial symptoms of the disease lead to a delay in the initiation of treatment, resulting in accumulative morbidity. Thus, there is a dire necessity to create more awareness. Furthermore, additional multiple large-scale trials are needed to evaluate the long-term safety and efficacy of velmanase alfa.
Prediction of early functional outcomes in patients after robotic-assisted total knee arthroplasty: a nomogram prediction model
Authors: Duan Xudong , Zhao Yiwei , Zhang Jiewen , Kong Ning , Cao Ruomu , Guan Huanshuai , Li Yiyang , Wang Kunzheng , Yang Pei , Tian Run
Published: June 2023

Background:

Robotic-assisted total knee arthroplasty (RA-TKA) is becoming more and more popular as a treatment option for advanced knee diseases due to its potential to reduce operator-induced errors. However, the development of accurate prediction models for postoperative outcomes is challenging. This study aimed to develop a nomogram model to predict the likelihood of achieving a beneficial functional outcome. The beneficial outcome is defined as a postoperative improvement of the functional Knee Society Score (fKSS) of more than 10 points, three months after RA-TKA by early collection and analysis of possible predictors.

Methods:

This is a retrospective study on 171 patients who underwent unilateral RA-TKA at our hospital. The collected data included demographic information, preoperative imaging data, surgical data, and preoperative and postoperative scale scores. Participants were randomly divided into a training set (N=120) and a test set (N=51). Univariate and multivariate logistic regression analyses were employed to screen for relevant factors. Variance Inflation Factor (VIF) was used to investigate for variable collinearity. The accuracy and stability of the models were evaluated using calibration curves with the Hosmer-Lemeshow goodness-of-fit test, consistency index (C-index) and receiver operating characteristic (ROC) curves.

Results:

Predictors of the nomogram included preoperative Hip-Knee-Ankle (HKA) angle deviation, preoperative 10-cm visual analogue scale (VAS) score, preoperative fKSS score and preoperative range of motion (ROM). Collinearity analysis with demonstrated no collinearity among the variables. The C-index values for the training and test sets were 0.908 and 0.902, respectively. Finally, the area under the ROC curve was 0.908 (95% CI 0.846-0.971) in the training set and 0.902 (95% CI 0.806-0.998) in the test set.

Conclusion:

A nomogram model was designed hereby aiming to predict the functional outcome three months after RA-TKA in patients. Rigorous validation showed that the model is robust and reliable. The identified key predictors include preoperative HKA angle deviation, preoperative VAS score, preoperative fKSS score, and preoperative ROM. These findings have major implications for improving therapeutic interventions and informing clinical decision-making in patients undergoing RA-TKA.
Effect of laparoscopic sleeve gastrectomy on mobilization of site-specific body adipose depots: a prospective cohort study
Authors: Cui Beibei , Duan Junhong , Zhu Liyong , Wang Guohui , Sun Xulong , Su Zhihong , Liao Yunjie , Yi Bo , Li Pengzhou , Li Weizheng , Song Zhi , Li Zheng , Tang Haibo , Rong Pengfei , Zhu Shaihong
Published: June 2023

Background:

Effect of bariatric surgery on mobilization of site-specific body adipose depots is not well investigated. Herein, we conducted a prospective cohort study to assess whether bariatric surgery can differentially affect specific fat storage pools and to further investigate correlations between site-specific fat mobilization and clinical outcomes.

Materials and Methods:

In this single-center prospective cohort study, 49 participants underwent laparoscopic sleeve gastrectomy (LSG) from 24 May 2022 to 20 October 2022 and underwent magnetic resonance imaging to estimate subcutaneous fat area (SFA), visceral fat area (VFA), hepatic and pancreatic proton density fat fraction (PDFF) at baseline and 3 months after surgery. The protocol for this study was registered on clinicaltrials.gov.

Results:

Among 49 patients who met all inclusion criteria, the median (interquartile range [IQR]) age was 31.0 (23.0–37.0) years, the median (IQR) body mass index was 38.1 (33.7–42.2) kg/m2 and 36.7% were male. Median (IQR) percentage hepatic PDFF loss was the greatest after bariatric surgery at 68.8% (47.3%–79.7%), followed by percentage pancreatic PDFF loss at 51.2% (37.0%–62.1%), percentage VFA loss at 36.0% (30.0%–42.4%), and percentage SFA loss at 22.7% (17.2%–32.4%) (P<0.001). By calculating Pearson correlation coefficient and partial correlation coefficient, the positive correlations were confirmed between change in VFA and change in glycated hemoglobin (r=0.394, P=0.028; partial r=0.428, P=0.042) and between change in hepatic PDFF and change in homeostatic model assessment of insulin resistance (r=0.385, P=0.025; partial r=0.403, P=0.046).

Conclusions:

LSG preferentially mobilized hepatic fat, followed by pancreatic fat and visceral adipose tissue (VAT), while subcutaneous adipose tissue was mobilized to the least extent. Reduction in VAT and hepatic fat is independently associated with the improvement of glucose metabolism after LSG.
A Comprehensive Program to Improve Treatment of Precancerous Cervical Lesions in the Rio Grande Valley of Texas
Authors: Varon Melissa , Salcedo Mila Pontremoli , Fellman Bryan , Troisi Catherine , Gowen Rose , Daheri Maria , Rodriguez Ana M. , Toscano Paul , Guerra Laura , Gasca Monica , Cavazos Blanca , Marin Elena , Fisher-Hoch Susan , Fernandez Maria E. , Reininger Belinda , Ruosha Li , Baker Ellen , Schmeler Kathleen
Published: June 2023

Objective:

To assess the impact of a multicomponent intervention in women with cervical dysplasia who were treated with loop electrosurgical excision procedure (LEEP), as well as the time between colposcopy and treatment.

Design:

Retrospective cohort study.

Intervention:

Clinic participation in a multicomponent cervical cancer prevention program that included community outreach, patient in-reach, and navigation, as well as provider capacity building with in-person training and ongoing telementoring through Project ECHO.

Main Outcome Measures:

Medical records were reviewed to evaluate women with cervical dysplasia undergoing treatment with LEEP within 90 days of colposcopy, as well as time between colposcopy and treatment. Baseline data from year 1 were compared with each subsequent year of implementation. Additional variables examined included patient's age, history of abnormal screening results, and percentage of families living below poverty line based on county of residence, parity, and clinic site. We performed logistic regression and multiple linear regression analyses to assess the programmatic impact in the outcomes of interest by year of program implementation.

Results:

A total of 290 women were included in the study. The proportion of women undergoing treatment within 90 days of colposcopy increased from 76.2% at baseline to 91.3% in year 3 and 92.9% in year 4 of program implementation. The odds of undergoing treatment within 90 days were 5.11 times higher in year 4 of program implementation than at baseline. The mean time between colposcopy and LEEP decreased from 62 days at baseline to 45 days by year 4 of program implementation.

Conclusions:

Implementation of our multicomponent cervical cancer prevention program increased the proportion of women undergoing LEEP within 90 days of colposcopy and decreased the time between colposcopy and LEEP. This program has the potential to support cervical cancer prevention efforts and could be implemented in other low-resource settings.
Anticoagulation in emergency general surgery: Who bleeds more? The EAST multicenter trials ACES study
Authors: O’Meara Lindsay , Zhang Ashling , Baum Jeffrey N. , Cooper Amanda , Decker Cassandra , Schroeppel Thomas , Cai Jenny , Cullinane Daniel C. , Catalano Richard D. , Bugaev Nikolay , LeClair Madison J. , Feather Cristina , McBride Katherine , Sams Valerie , Leung Pak Shan , Olafson Samantha , Callahan Devon S. , Posluszny Joseph , Moradian Simon , Estroff Jordan , Hochman Beth , Coleman Natasha L. , Goldenberg-Sandau Anna , Nahmias Jeffry , Rosenbaum Kathryn , Pasley Jason D. , Boll Lindsay , Hustad Leah , Reynolds Jessica , Truitt Michael , Vesselinov Roumen , Ghneim Mira
Published: June 2023

BACKGROUND

While direct oral anticoagulant (DOAC) use is increasing in the Emergency General Surgery (EGS) patient population, our understanding of their bleeding risk in the acute setting remains limited. Therefore, the objective of this study was to determine the prevalence of perioperative bleeding complications in patients using DOACs versus warfarin and AP therapy requiring urgent/emergent EGS procedures (EGSPs).

METHODS

This was a prospective observational trial, conducted between 2019 and 2022, across 21 centers. Inclusion criteria were 18 years or older, DOAC, warfarin/AP use within 24 hours of requiring an urgent/emergent EGSP. Demographics, preoperative, intraoperative, and postoperative data were collected. ANOVA, χ2, and multivariable regression models were used to conduct the analysis.

RESULTS

Of the 413 patients enrolled in the study, 261 (63%) reported warfarin/AP use and 152 (37%) reported DOAC use. Appendicitis and cholecystitis were the most frequent indication for operative intervention in the warfarin/AP group (43.4% vs. 25%, p = 0.001). Small bowel obstruction/abdominal wall hernias were the main indication for operative intervention in the DOAC group (44.7% vs. 23.8%, p = 0.001). Intraoperative, postoperative, and perioperative bleeding complications and in-hospital mortality were similar between the two groups. After adjusting for confounders, a history of chemotherapy (odds ratio [OR], 4.3; p = 0.015) and indication for operative intervention including occlusive mesenteric ischemia (OR, 4.27; p = 0.016), nonocclusive mesenteric ischemia (OR, 3.13; p = 0.001), and diverticulitis (OR, 3.72; p = 0.019) were associated with increased perioperative bleeding complications. The need for an intraoperative transfusion (OR, 4.87; p < 0.001), and intraoperative vasopressors (OR, 4.35; p = 0.003) were associated with increased in-hospital mortality.

CONCLUSION

Perioperative bleeding complications and mortality are impacted by the indication for EGSPs and patient's severity of illness rather than a history of DOAC or warfarin/AP use. Therefore, perioperative management should be guided by patient physiology and indication for surgery rather than the concern for recent antiplatelet or anticoagulant use.

LEVEL OF EVIDENCE

Prognostic and Epidemiologic; Level III.
The influence of early moderate prenatal alcohol exposure and maternal diet on offspring DNA methylation: a cross-species study
Authors: Bestry Mitchell , Larcombe Alexander N. , Kresoje Nina , Chivers Emily K , Bakker Chloe , Fitzpatrick James P , Elliott Elizabeth J , Craig Jeffrey M , Muggli Evelyne , Halliday Jane , Hutchinson Delyse , Buckberry Sam , Lister Ryan , Symons Martyn , Martino David
Published: June 2023

Alcohol consumption in pregnancy can affect genome regulation in the developing offspring but results have been contradictory. We employed a physiologically relevant murine model of short-term moderate prenatal alcohol exposure (PAE) resembling common patterns of alcohol consumption in pregnancy in humans. Early moderate PAE was sufficient to affect site-specific DNA methylation in new-born pups without altering behavioural outcomes in adult littermates. Whole-genome bisulfite sequencing of neonatal brain and liver revealed stochastic influence on DNA methylation that was mostly tissue-specific, with some perturbations likely originating as early as gastrulation. DNA methylation differences were enriched in non-coding genomic regions with regulatory potential indicative of broad effects of alcohol on genome regulation. Replication studies in human cohorts with fetal alcohol spectrum disorder suggested some effects were metastable at genes linked to disease-relevant traits including facial morphology, intelligence, educational attainment, autism, and schizophrenia. In our murine model, a maternal diet high in folate and choline protected against some of the damaging effects of early moderate PAE on DNA methylation. Our studies demonstrate that early moderate exposure is sufficient to affect fetal genome regulation even in the absence of overt phenotypic changes and highlight a role for preventative maternal dietary interventions.
Using CombiCells, a platform enabling titration and combinatorial display of cell surface ligands, to study T cell antigen sensitivity by TCRs, CARs, and BiTEs
Authors: Patel Ashna , Andre Violaine , Eguiguren Sofia Bustamante , Barton Michael I. , Burton Jake , Denham Eleanor M. , Pettmann Johannes , Mørch Alexander M , Kutuzov Mikhail A. , Siller-Farfán Jesús A. , Dustin Michael L. , van der Merwe P. Anton , Dushek Omer
Published: June 2023

Understanding how cellular decisions by receptor/ligand interactions at cell/cell interface has been challenging because it is difficult to independently vary the surface density of multiple ligands. Here, we exploit the SpyCatcher/SpyTag split-protein system for rapid combinatorial display of native ligands on cells (Combicells). We use this platform to assess T cell antigen sensitivity and the impact of T cell co-stimulation/co-inhibition receptors. The TCR displayed much greater sensitivity to pMHC than CARs and BiTES did to CD19. While TCR sensitivity was greatly enhanced by CD2 ligand, CAR sensitivity to CD19 was primarily but more modestly enhanced by LFA-1 ligand. Lastly, we show that the PD-1/ligand engagement inhibited T cell activation triggered solely by TCR/pMHC interactions, as well as the amplified activation induced by CD2 and CD28 co-stimulation. The ability to easily produce cells with different concentrations and combinations of ligands should accelerate the study of receptor/ligand interactions at cell/cell interfaces.

Graphical abstract

One sentence summary

Using CombiCells, a platform for the combinatorial display of cell surface ligands, to compare T cell antigen sensitivity mediated by TCRs, CARs, and BiTEs and its dependence on co-stimulation/co-inhibition receptor ligands
The Plasminogen-Apple-Nematode (PAN) domain suppresses JA/ET defense pathways in plants
Authors: De Kuntal , Pal Debjani , Shanks Carly M. , Yates Timothy B. , Feng Kai , Jawdy Sara S. , Hassan Md Mahmudul , Prabhakar Pradeep K. , Yang Jeong-Yeh , Chapla Digantkumar , Moremen Kelley W. , Urbanowicz Breeanna , Binder Brad M , Muchero Wellington
Published: June 2023

Suppression of immune response is a phenomenon that enables biological processes such as gamete fertilization, cell growth, cell proliferation, endophyte recruitment, parasitism, and pathogenesis. Here, we show for the first time that the Plasminogen-Apple-Nematode (PAN) domain present in G-type lectin receptor-like kinases is essential for immunosuppression in plants. Defense pathways involving jasmonic acid and ethylene are critical for plant immunity against microbes, necrotrophic pathogens, parasites, and insects. Using twoSalix purpureaG-type lectin receptor kinases, we demonstrated that intact PAN domains suppress jasmonic acid and ethylene signaling in Arabidopsis and tobacco. Variants of the same receptors with mutated residues in this domain could trigger induction of both defense pathways. Assessment of signaling processes revealed significant differences between receptors with intact and mutated PAN domain in MAPK phosphorylation, global transcriptional reprogramming, induction of downstream signaling components, hormone biosynthesis and resistance toBotrytis cinerea. Further, we demonstrated that the domain is required for oligomerization, ubiquitination, and proteolytic degradation of these receptors. These processes were completely disrupted when conserved residues in the domain were mutated. Additionally, we have tested the hypothesis in recently characterizedArabidopsismutant which has predicted PAN domain and negatively regulates plant immunity against root nematodes.ern1.1mutant complemented with mutated PAN shows triggered immune response with elevated WRKY33 expression, hyperphosphorylation of MAPK and resistant to necrotrophic fungusBotrytis cinerea. Collectively, our results suggest that ubiquitination and proteolytic degradation mediated by the PAN domain plays a role in receptor turn-over to suppress jasmonic acid and ethylene defense signaling in plants.
Histone binding of ASF1 is required for fruiting body development, but not for genome stability in the filamentous fungusSordaria macrospora
Authors: Breuer Jan , Busche Tobias , Kalinowski Jörn , Nowrousian Minou
Published: June 2023

The highly conserved eukaryotic histone chaperone ASF1 is involved in the assembly and disassembly of nucleosomes during transcription, DNA replication and repair. It was the first chaperone discovered to be involved in all three of these processes. The filamentous fungusSordaria macrosporais one of only two multicellular organisms whereasf1deletions are viable, which makes it useful forin vivoanalysis of this central regulator of eukaryotic chromatin structure. Deletion ofasf1inS. macrosporaleads to sterility, a reduction of DNA methylation, and upregulation of genes that are usually weakly expressed in the wild type. Here, we focused on the functions of the highly conserved core and the divergent C-terminal tail of ASF1, studied the effects of ASF1 on histone modifications and tested its relevance for genomic stability. By Co-IP and complementation analysis we showed that substitutions of amino acid V94 or truncations of the C-terminal tail abolish histone binding and do not complement the sterile mutant phenotype. Δasf1 is sensitive to the DNA damaging agent MMS, while complementation strains, even those with non-histone-binding variants, regain wild type-like resistance. To aid in subsequent ChIP-seq and Hi-C analyses, we generated a chromosome-resolved genome assembly ofS. macrospora. ChIP-Seq analysis revealed a global increase of H3K27me3 in Δasf1, accompanied by a global decrease of H3K56ac. By using Hi-C we detected a tandem duplication of around 600 kb on chromosome 2 in the mutant. Crossing experiments indicated linkage between the viability of Δasf1 strains and the presence of the duplication.

Importance

Histone chaperones are proteins that are involved in nucleosome assembly and disassembly and can therefore influence all DNA-dependent processes including transcription, DNA replication and repair. ASF1 is a histone chaperone that is conserved throughout eukaryotes. In contrast to most other multicellular organisms, a deletion mutant ofasf1in the fungusSordaria macrosporais viable; however, the mutant is sterile. In this study, we could show that the histone binding ability of ASF1 is required for fertility inS. macrospora, whereas the function of ASF1 in maintenance of genome stability does not require histone binding. We also showed that the histone modifications H3K27me3 and H3K56ac are misregulated in the Δasf1 mutant. Furthermore, we identified a large duplication on chromosome 2 of the mutant strain that is genetically linked to the Δasf1 allele present on chromosome 6, suggesting that viability of the mutant might depend on the presence of the duplicated region.
Transcriptome of left ventricle and sinoatrial node in young and old C57 mice
Authors: Qu Jia-Hua , Tarasov Kirill V. , Tarasova Yelena S. , Chakir Khalid , Lakatta Edward G.
Published: June 2023

Advancing age is the most important risk factor for cardiovascular diseases (CVDs). Two types of cells within the heart pacemaker, sinoatrial node (SAN), and within the left ventricle (LV) control two crucial characteristics of heart function, heart beat rate and contraction strength. As age advances, the heart’s structure becomes remodeled, and SAN and LV cell functions deteriorate, thus increasing the risk for CVDs. However, the different molecular features of age-associated changes in SAN and LV cells have never been compared in omics scale in the context of aging. We applied deep RNA sequencing to four groups of samples, young LV, old LV, young SAN and old SAN, followed by numerous bioinformatic analyses. In addition to profiling the differences in gene expression patterns between the two heart chambers (LV vs. SAN), we also identified the chamber-specific concordant or discordant age-associated changes in: (1) genes linked to energy production related to cardiomyocyte contraction, (2) genes related to post-transcriptional processing, (3) genes involved in KEGG longevity regulating pathway, (4) prolongevity and antilongevity genes recorded and curated in the GenAge database, and (5) CVD marker genes. Our bioinformatic analysis also predicted the regulation activities and mapped the expression of upstream regulators including transcription regulators and post-transcriptional regulator miRNAs. This comprehensive analysis promotes our understanding of regulation of heart functions and will enable discovery of gene-specific therapeutic targets of CVDs in advanced age.
Metal Ions and their Effects on Antimicrobial Resistance Development in Wastewater
Authors: Sutradhar Indorica , Kalyan Prinjali , Chukwu Kelechi , Abia Akebe Luther King , Mbanga Joshua , Essack Sabiha , Hamer Davidson H. , Zaman Muhammad H.
Published: June 2023

Antimicrobial resistance (AMR) is a global health challenge and there is increasing recognition of the role of the environment, particularly wastewater, in the development and spread of AMR. Although trace metals are common contaminants in wastewater, the quantitative effects of trace metals on AMR in wastewater settings remain understudied. We experimentally determined the interactions between common antibiotic residues and metal ions found in wastewater and investigated their effects on the development of antibiotic resistance inEscherichia coliover time. These data were then used to expand on a previously developed computational model of antibiotic resistance development in continuous flow settings to incorporate the effects of trace metals acting in combination with multiple antibiotic residues. We found that the common metal ions, copper and iron, interact with both ciprofloxacin and doxycycline at wastewater relevant concentrations. This can significantly affect resistance development due to antibiotic chelation of the metal ions causing a reduction in the antibiotics’ bioactivity. Furthermore, modeling the effect of these interactions in wastewater systems showed the potential for metal ions in wastewater to significantly increase the development of antibiotic resistantE. colipopulations. These results demonstrate the need to quantitatively understand the effects of trace metal-antibiotic interactions on AMR development in wastewater.
QRS Detection by Rules Based Multiple Channel Combinatorial Optimization
Authors: Hopenfeld Bruce
Published: June 2023

A multiple channel QRS detector is described. Separately for each channel, the detector generates sequences of peaks and statistically scores them according to: 1) peak prominence; 2) temporal regularity; 3) peak shape similarity; and 4) number of skipped beats. In the case of unstructured rhythms, the temporal regularity score is null and does not contribute to sequence quality. If at least one winning score from any channel exceeds a quality threshold, multi-channel sequences are generated from the winning sequences’ peaks and scored according to the above measures and peak time coherence across channels. The winning multi-channel sequence is then selected. The algorithm was applied to both channels of the MIT-BIH Arrhythmia Database. Over the entire database, the sensitivity (SE) and positive predictive value (PPV) were 99.93% and 99.96% respectively. For record 203, generally considered the most difficult one in the database, the SE and PPV were 99.80% and 99.76% respectively. The present algorithm fits within the framework of a previously described algorithm that can detect sinus rhythm in high noise conditions (e.g. waist based textile electrode recordings of a jogging subject).
Unbiased single-cell morphology with self-supervised vision transformers
Authors: Doron Michael , Moutakanni Théo , Chen Zitong S. , Moshkov Nikita , Caron Mathilde , Touvron Hugo , Bojanowski Piotr , Pernice Wolfgang M. , Caicedo Juan C.
Published: June 2023

Accurately quantifying cellular morphology at scale could substantially empower existing single-cell approaches. However, measuring cell morphology remains an active field of research, which has inspired multiple computer vision algorithms over the years. Here, we show that DINO, a vision-transformer based, self-supervised algorithm, has a remarkable ability for learning rich representations of cellular morphology without manual annotations or any other type of supervision. We evaluate DINO on a wide variety of tasks across three publicly available imaging datasets of diverse specifications and biological focus. We find that DINO encodes meaningful features of cellular morphology at multiple scales, from subcellular and single-cell resolution, to multi-cellular and aggregated experimental groups. Importantly, DINO successfully uncovers a hierarchy of biological and technical factors of variation in imaging datasets. The results show that DINO can support the study of unknown biological variation, including single-cell heterogeneity and relationships between samples, making it an excellent tool for image-based biological discovery.