bluuebunny/crossref_metadata_2025 huggingface dataset:
Penicillin-binding protein redundancy in
Bacillus subtilis
enables growth during alkaline shock
Authors: Mitchell Stephanie L. , Kearns Daniel B. , Carlson Erin E.
Published: December 2023

Penicillin-binding proteins (PBPs) play critical roles in cell wall construction, cell shape maintenance, and bacterial replication. Bacteria maintain a diversity of PBPs, indicating that despite their apparent functional redundancy, there is differentiation across the PBP family. Apparently-redundant proteins can be important for enabling an organism to cope with environmental stressors. In this study, we evaluated the consequence of environmental pH on PBP enzymatic activity in
Bacillus subtilis
. Our data show that a subset of PBPs in
B. subtilis
change activity levels during alkaline shock and that one PBP isoform is rapidly modified to generate a smaller protein (i.e., PBP1a to PBP1b). Our results indicate that a subset of the PBPs are favored for growth under alkaline conditions, while others are readily dispensable. Indeed, we found that this phenomenon could also be observed in
Streptococcus pneumoniae
, implying that it may be generalizable across additional bacterial species and further emphasizing the evolutionary benefit of maintaining many, seemingly-redundant periplasmic enzymes.

IMPORTANCE

Microbes adapt to ever-changing environments and thrive over a vast range of conditions. While bacterial genomes are relatively small, significant portions encode for “redundant” functions. Apparent redundancy is especially pervasive in bacterial proteins that reside outside of the inner membrane. While conditions within the cytoplasm are carefully controlled, those of the periplasmic space are largely determined by the cell’s exterior environment. As a result, proteins within this environmentally exposed region must be capable of functioning under a vast array of conditions, and/or there must be several similar proteins that have evolved to function under a variety of conditions. This study examines the activity of a class of enzymes that is essential in cell wall construction to determine if individual proteins might be adapted for activity under particular growth conditions. Our results indicate that a subset of these proteins are preferred for growth under alkaline conditions, while others are readily dispensable.
Disturbance and recovery of physical elements of habitat in relation to post-wildfire channel sedimentation, southern California Transverse Ranges
Authors: Florsheim Joan L. , Chin Anne
Published: December 2023

Sedimentation after wildfire is a profound disturbance to the biogeomorphic character of fluvial systems. Despite this significant alteration, field data focusing on the geomorphic processes and bed morphology that form the physical structure of habitat are limited, especially over a longer-term perspective. We report results of detailed field studies following two wildfires in the same steep fluvial system in the southern California Transverse Ranges three decades apart. Substantial channel sedimentation during storms following both fires altered physical elements of habitat, which included bed elevation, step height and spacing, pool depth and spacing, grain-size distribution (D84), and transport capacity (τo/τc). The postfire sediment deposits buried bedforms, decreased D84, and increased τo/τc by an order of magnitude. Incision during subsequent storms initiated recovery that depended on the attributes of post-wildfire climate variability that characterize the semiarid Mediterranean-type environment. Step-pool bedforms reappeared or reformed during the decades between wildfires as the relatively fine gravel-sized post-wildfire sediment was transported downstream, thus reestablishing the physical elements of habitat characterizing the dynamic system.
Safety, resource use and nutritional content of home-blended diets in children who are gastrostomy fed: findings from ‘YourTube’ – a prospective cohort study
Authors: Fraser Lorna K , Bedendo Andre , O’Neill Mark , Taylor Jo , Hackett Julia , Horridge Karen Alice , Cade Janet , Richardson Gerry , Phung Han , McCarter Alison , Hewitt Catherine Elizabeth
Published: December 2023

Objective

To assess the risks, benefits and resource implications of using home-blended food in children with gastrostomy tubes compared with currently recommended formula feeds.

Design

This is a cohort study. Data were collected at months 0, 12 and 18 from parents and clinicians using standardised measures.

Setting

32 sites across England: 28 National Health Service trusts and 4 children’s hospices.

Patients

Children aged 6 months–18 years who were gastrostomy fed.

Main outcome measure

The main outcome measure was the PedsQL Gastrointestinal Symptoms Scales score. Secondary outcomes included quality of life, sleep (child, parent), dietary intake, anthropometry, healthcare usage, safety outcomes and resource use.

Results

180 children and families completed the baseline data collection, with 134 (74%) and 105 (58%) providing follow-up data at 12 and 18 months. There were fewer gastrointestinal (GI) symptoms at all time points in the home-blended diet group, but there was no difference in change over time within or between the groups. The nutritional intake of those on a home-blended diet had higher calories per kilogram and fibre, and both home-blended and formula-fed children have values above the dietary reference values for most micronutrients. Safety outcomes were similar between groups and over time. The total costs to the statutory sector were higher among children who were formula fed, but the costs of purchasing special equipment for home-blended food and the total time spent on childcare were higher for families with home-blended diet.

Conclusions

Children who are gastrostomy fed a home-blended diet have similar safety profile, adequate nutritional intake and lower burden of GI symptoms than formula-fed children.

Trial registration numberISRCTN13977361.
Improvement of persistent anuria in severe myocardial infarction: the potential role of Impella 5.5 as a bridge to decision
Authors: Suzuki Toshiaki , Sugiura Ryo
Published: December 2023

A man in his 40s with ST-segment elevation myocardial infarction complicating cardiogenic shock was transferred to our hospital. Emergent percutaneous coronary intervention for the left anterior descending and left circumflex arteries supported with Impella CP was performed. However, his cardiac function was severely impaired, and anuria developed, necessitating continuous renal replacement therapy (CRRT). After Impella CP was removed on day 6, the patient remained dependent on inotropes and CRRT. Following volume reduction to manage pulmonary congestion, symptoms of low perfusion appeared. Then, Impella 5.5 was inserted on day 38 as a bridge to decision. On day 52, the urine volume reached >2000 mL/day, and CRRT was discontinued. On day 56, the patient was transferred to a certified facility for left ventricular assist device implantation or heart transplantation. This case suggests the potential of Impella 5.5 as a bridge to decision in patients with organ failure caused by low cardiac output.
Bacillary layer detachment as an inflammatory biomarker in toxoplasmosis retinochoroiditis: serial evolution on optical coherence tomography
Authors: Desai Arjun , Tyagi Mudit
Published: December 2023

We describe the clinical course and serial evolution of bacillary layer detachment (BALAD) on optical coherence tomography (OCT) in toxoplasmosis retinochoroiditis and its importance as an inflammatory biomarker. Colour fundus photography and swept-source OCT of the BALAD were done at the time of presentation and subsequently at 1 week, 2 weeks, 4 weeks and at 11 weeks. Treatment involved oral trimethoprim (160 mg) + sulphamethoxazole (800 mg) two times per day, started at presentation for 2 months. Oral prednisolone was started after 1 week at a dose of 50 mg a day and tapered weekly over the next 5 weeks. The BALAD initially increased after starting treatment with trimethoprim-sulphamethoxazole and regressed within 1 week after initiation of oral prednisolone. Best corrected visual acuity improved to 20/40 from 20/160 at presentation (Snellen equivalent). This suggests that BALAD is an indicator of an acute inflammatory event and the accumulated fluid is secondary to retinal and choroidal inflammation.
Social justice in undergraduate medical education: a meta-synthesis of learners’ perspectives
Authors: Khan Nagina , Rogers Anne , Serafimov Alex , Sehdev Simran , Hickman Marie , Sri Anna , Dave Subodh
Published: December 2023

Introduction

The COVID-19 pandemic has illuminated disparities and inequities in healthcare globally, making it a necessity to identify, and address social and structural determinants of people’s everyday lives. Medical schools and education need to respond to and address social justice in undergraduate education. Social justice in medical education has the potential to be a foundational block to support the initiatives that have or are being implemented in our health systems.

Methods

We carried out a meta-synthesis and used an interpretative approach for the analysis. Searches were conducted of three databases: PsycINFO, Embase and Medline and were carried out in May 2021. We excluded articles that were not related to undergraduate medical students. The aim of this review was to explore literature on SJ teaching to elicit the experiences of learners to inform future SJ teaching and curriculum.

Results

Using meta-synthesis methodology, four themes emerged: personal growth of learners and professional identities; developing commitment to working with marginalised populations in their environments; integrating traditional clinical skills with advocacy, interests in human rights and SJ work; learning processes and methods.

Conclusions

Findings confirm that SJ in undergraduate medical education has an essential role. However, social justice in medical education was understood as a non-essential piece of professionalism, or as something to be learnt in the abstract method rather than as a part of everyday practice realities. Our findings suggest that creating globally competent doctors through a globally equivalent curriculum, which is balanced and with a locally invested training programme could lead to a supply or workforce that is fit for purpose for local populations.
‘Your CV looks amazing but I am sorry, you didn’t get the job’: analysing experiences of global majority physiotherapists aspiring to and working at consultant level practice in the UK
Authors: Walumbe Jackie , Wright Andrea , Adonis Adine , Hammond John , Ramdharry Gita
Published: December 2023

Introduction

Effective leadership shapes organisational culture to deliver world class healthcare. Racially minoritised individuals rarely access opportunities leading to leadership positions. This paper expands on themes from qualitative research which explored experiences of qualified physiotherapists from racially minoritised backgrounds aspiring to (or working at) consultant level and codesigned recommendations that challenge inequitable practices which perpetuate unearned privilege.

Methods

The study used critical discourse analysis to understand the experiences of aspirants. Participants were recruited purposively using snowball sampling via professional diversity networks and social media. Semistructured interviews were conducted remotely. Externally facilitated focus groups supported cocreating research outcomes and strategies for action. Secondary analysis extends our initial analysis to focus on two themes, critically considering these in the context of the role of leadership.

Results

Data drawn from 17 participants from self-identified racialised groups who were either in consultant level positions, or aspiring to be, were included in secondary analysis. Analysis identified structural racism as an enduring social wrong, existing within different levels of organisations. Managerial ‘gatekeepers’ created barriers to career progression by not recognising skills, knowledge and experience. Pathways to career progression were hidden and unwieldy, operated by managers in ways that restricted leadership opportunities disproportionately to white peers. These challenges created a sense of ‘un-belonging’ resulting in negative health impacts.

Conclusion

Gatekeepers maintaining racist cultural practices and policies were key in upholding the hegemonic status quo. Collective strategies enabled a sense of ontological belonging and empowerment for participants and may be helpful for those experiencing similar concerns in their workplaces.
Burden of systemic lupus erythematosus in clinical practice: baseline data from the SLE Prospective Observational Cohort Study (SPOCS) by interferon gene signature
Authors: Arnaud Laurent , Furie Richard , Morand Eric F , Aringer Martin , Peschken Christine , Desta Barnabas , Rapsomaniki Eleni , Hedberg Jonatan , Knagenhjelm Jacob , Seo Caroline , Grünfeld Eén Tina , Sorrentino Alessandro , Tummala Raj , Stirnadel-Farrant Heide A , Ding Bo
Published: December 2023

Objective

The longitudinal Systemic Lupus Erythematosus Prospective Observational Cohort Study (SPOCS) aims to assess SLE disease course overall and according to type I interferon 4 gene signature (IFNGS). Here, we describe SPOCS patient characteristics by IFNGS and baseline disease activity.

Methods

SPOCS (NCT03189875) is an international study of patients with SLE according to Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) criteria. Enrolled patients from 135 centres in 8 countries were followed biannually for ≤3 years from June 2017 to November 2022. Baseline demographics, disease characteristics, organ system involvement/damage and flares were analysed descriptively according to SLE Disease Activity Index-2000 score (SLEDAI-2K <10/≥10) and IFNGS status (high/low).

Results

The study population (n=823) was 93.2% female, with mean (SD) age 45.3 (13.9) years and 11.1 (9.2) years since diagnosis; 52.4% had baseline SLICC/ACR Damage Index score ≥1. Patients with SLEDAI-2K scores ≥10 (241 of 584, 41.3%) vs <10 were younger (mean 42.8 (13.7) vs 46.6 (14.2) years; nominal p=0.001), had shorter SLE duration (10.4 (8.6) vs 12.4 (9.6) years; nominal p=0.012) and more severe flares (12.9% vs 5.3%; nominal p=0.001). IFNGS-high patients (522 of 739, 70.6%) were younger than IFNGS-low patients at first SLE manifestation (30.0 (12.7) vs 36.8 (14.6) years; nominal p<0.001). Proportions of IFNGS-high patients differed according to race (nominal p<0.001), with higher proportions among Asian (83.3%) and black (86.5%) versus white patients (63.5%). Greater proportions of IFNGS-high versus IFNGS-low patients had haematological (12.6% vs 4.1%), immunological (74.4% vs 45.6%) or dermal (69.7% vs 62.2%) involvement.

Conclusions

We identified key characteristics of patients with high disease activity and/or elevated type I IFN signalling, populations with SLE with high unmet needs. Baseline SLEDAI-2K ≥10 was associated with shorter disease duration and more severe flares. IFNGS-high patients were younger at diagnosis and had distinct patterns of organ involvement, compared with IFNGS-low patients.
An intellectual gap in root research on major crops of the Canadian Prairies
Authors: Gorim Linda Yuya
Published: December 2023

Prairie cropping systems face several challenges, including high input costs and climate change. Research to address these challenges has focused on above-ground agronomic parameters while completely ignoring the role roots play below ground. The objectives of this review study are to (i) synthesize past root studies carried out in the Canadian Prairies, (ii) provide a context for prairie root research, and (iii) identify gaps for future research. This review reports that root architectural traits of major crops have been assessed under field and greenhouse conditions in soil, artificial media, and a mixture of both soil and media, mostly under natural/well-watered and drought conditions. Several root traits have been compared for major crops grown with respect to moisture levels and nutrient uptake. A dearth of research exists on the complex relationship between root traits, soil microbiome, nutrient uptake, carbon sequestration, and photosynthetic efficiency. No studies were found relating root traits, fertilizer placement, and nitrogen and water use efficiencies, carbon sequestration, soil microbiome dynamics, and common root diseases. This review also reports that more research and funding are needed to exploit the benefits that root research will bring to further sustainability goals and ensure food security in the Canadian Prairies.
On torsion contribution to chiral anomaly via Nieh–Yan term
Authors: M. Rasulian Ida , Torabian Mahdi
Published: December 2023

In this note we present a solution to the question of whether or not, in the presence of torsion, the topological Nieh–Yan term contributes to chiral anomaly. The integral of Nieh–Yan term is non-zero if topology is non-trivial; the manifold has a boundary or vierbeins have singularities. Noting that singular Nieh–Yan term could be written as a sum of delta functions, we argue that the heat kernel expansion cannot end at finite steps. This leads to a sinusoidal dependence on the Nieh–Yan term and the UV cut-off of the theory (or alternatively the minimum length of spacetime). We show this ill-behaved dependence can be removed if a quantization condition on length scales is applied. It is expected as the Nieh–Yan term can be derived as the difference of two Chern class integrals (i.e. Pontryagin terms). On the other hand, in the presence of a cosmological constant, we find that indeed the Nieh–Yan term contributes to the index with a dimensionful anomaly coefficient that depends on the de Sitter length or equivalently inverse Hubble rate. We find similar result in thermal field theory where the anomaly coefficient depends on temperature. In both examples, the anomaly coefficient depends on IR cut-off of the theory. Without singularities, the Nieh–Yan term can be smoothly rotated away, does not contribute to topological structure and consequently does not contribute to chiral anomaly.
Soft theorems and memory effects at finite temperatures
Authors: Solanki Divyesh N. , Bhattacharjee Srijit
Published: December 2023

We study the soft theorems for photons and gravitons at finite temperatures using the thermofield dynamics approach. The soft factors lose universality at finite temperatures as the soft amplitudes depend on the nature (or spin) of the particles participating in the scattering processes. However, at low temperatures, a universal behavior is observed in the cross-section of the soft processes. Further, we obtain the thermal contribution to the electromagnetic and gravitational memory effects and show that they are related to the soft factors consistently. The expected zero temperature results are obtained from the soft factors and memories. The thermal effects in soft theorems and memories seem to be sensitive to the spin of the particles involved in scattering.
Nash Equilibrium in Fuzzy Random Bi-Matrix Games
Authors: Achemine Farida , Larbani Moussa
Published: December 2023

Most of the existing works on games under uncertainty consider only one type of uncertainty: fuzzy, random, rough, etc. However, in real-world games, it often happens that randomness and fuzziness simultaneously affect the interaction between players and their payoffs. Investigating fuzzy random games is challenging as it is difficult to express the preferences of players in the presence of two different types of uncertainty. This paper presents a new approach to games involving randomness and fuzziness. Specifically, we consider bi-matrix games where the payoffs are fuzzy random variables. Using probability and possibility measures, we formulate related fuzzy chance-constrained games. Then, we introduce Nash equilibrium for these games. Next, we establish sufficient conditions for the existence of this equilibrium. Further, the problem of its computing is formulated as a nonlinear complementarity problem. Finally, examples of market competition games and pollution management are given to illustrate the application potential of the proposed approach. The novelty and advantage of this work are that it grants the players the freedom to choose the probability and possibility confidence/satisfaction levels at which they want Nash equilibrium to be, and equilibrium computation is simpler compared to existing approaches to fuzzy random bi-matrix games.
AI Powers the Digital Economy
Authors: Riley Jeff
Published: December 2023

Artificial Intelligence (AI) has had a profound impact on the digital economy. We explore that impact, and outline how AI technologies, including machine learning and big data analytics, have revolutionized sectors such as eCommerce, finance, supply chain, logistics, and manufacturing. The integration of AI has led to increased efficiency, personalized customer experiences, and significant transformations in traditional business models. We anticipate continued growth in AI's influence on the digital economy, with the Internet of Things contributing to even more data-driven advancements. AI is a driving force powering and shaping the future of the digital economy.
Assessment of Health Risks in Wheat Crop Irrigated by Manka Canal, Dera Ghazi Khan, Pakistan
Authors: Hassan Muhammad Anwar ul , Javied Sabiha , Riaz Umair , Saleh Muneera A. , Alamer Khalid H. , Siddique Naila , Aslam Ambreen , Noor Nabeela , Zaman Qamar uz
Published: December 2023

Background. Manka canal’s metal concentration rises from human activities’ garbage. Untreated water from the canal is used by farmers for local crop irrigation. Immediate action is crucial to assess heavy metal levels and ensure soil suitability for agriculture as metal pollution persists. Purpose. The current study was conducted to assess the health risks associated with metal pollution at Manka Canal, Dera Ghazi Khan. Methods. A total of eighty-four wastewater, soil, and wheat samples were collected from study areas. The collected samples were analyzed for heavy metals (Cd, Cu, Fe, Mn, Ni, Pb, and Zn) using a flame atomic absorption spectrometer (FAAS). Results. The significant findings of the study revealed that the concentration of heavy metals in most of the collected samples of soil, water, and wheat was above the World Health Organization (WHO) permissible limits. The mean concentrations of Cd, Cu, Mn, Ni, Pb, and Zn were at relatively higher concentrations, i.e., 4.88, 22.03, 38.2, 89.2, 19.62, and 67.9 mg/kg, respectively, in collected wheat samples. The soil and irrigation water quality metrics had values that exceeded the acceptable thresholds, rendering them unfit for agricultural use. The local community faces an elevated health risk index for both children and adults due to the consumption of wheat crop as HRI is greater than 1 for nonessential elements like Cd and Pb. Conclusion. The study suggested that wastewater irrigation leads to the accumulation of heavy metals in foodstuffs, causing potential health risks to consumers. The gradual accumulation of these contaminants in biological systems finally gives rise to severe health-related issues. Therefore, it is crucial to implement robust wastewater treatment processes and stringent quality control measures to minimize health risks associated with the consumption of crops grown using reclaimed water. Prior to irrigating crops like wheat and vegetables, it is strongly advised to treat municipal wastewater to prevent soil and dietary toxicity from heavy metals.
Controlled Voltage of Hot Snare Polypectomy Device in Electrosurgical Device
Authors: Olalere Saidi O. , Choi JungHun
Published: December 2023

The study aimed to understand the working procedure of the Olympus PSD-30 Electrosurgical Unit, in which a high-frequency alternating current measures the voltage and power output from the unit when used for a surgical operation to determine the extent of tissue damage. In examining this, power and voltage were analyzed using a stopwatch output; then with an Arduino time-based for 1, 2, and 3 seconds to understand the different modes of the cut and coagulation feedback with an RCC circuit used to mimic the human body. This shows a pattern in which the feedback power increases and the voltage decreases as the cut and coagulation mode increases. The percentage between the stopwatch and Arduino is 29% for the 1 and 2 seconds. With this information, Arduino Uno timing was used to experiment with the device for the different power settings for both the cut and coagulation modes from 2 W to 50 W at 5 W intervals. Based on each trial, the signal was measured for a magnitude of 1 Vpp, and the crest factor obtained was 1.5 with a voltage of 1.088 V and 1.0519 V for both the LabView and oscilloscope, respectively, for the electrosurgical unit of 350 kHz. The power control gives 0.4 W, 2.04 W, and 3.01 W for the power peak at 1, 2, and 3 seconds for the 50 W cut mode of the electrosurgical devices.
Changing Surgical Aortic Valve Size and Choices in the Transcatheter Aortic Valve Replacement Era
Authors: Gertz Zachary M. , Strobel Raymond J. , Wisniewski Alex M. , Fonner Clifford E. , Speir Alan , Teman Nicholas R. , Quader Mohammed
Published: December 2023

Objective. The adoption of transcatheter aortic valve replacement (TAVR) has changed the profile of patients referred for surgical aortic valve replacement (SAVR) and drawn more attention to valve sizing and durability. We examined the influence of TAVR on SAVR practice. Methods. Using a statewide database, we evaluated all isolated SAVRs, categorized into three eras: pre-TAVR (2008 to 2011), early TAVR (2012 to 2015), and current-TAVR (2016 to 2022). The primary outcomes of interest were changes in prosthetic valve size and the percentage of mechanical valves used between time periods. Results. There were 6,445 patients included. SAVR volume declined in the current era. Valve size increased over time. In the pre-TAVR era, 41% of patients received a valve smaller than 23 mm, which declined to 33% in the early TAVR era, then to 22% in the current era (p < 0.001 for all). The year of surgery was significantly associated with larger valve selection even after controlling for patient characteristics. Annular enlargement rose in the current-TAVR era (p < 0.001). The use of mechanical valves rose in the current era (p < 0.001 compared to early TAVR). Regression analysis showed that the year of surgery was not predictive of mechanical valve use, suggesting that changes in practice were driven by patient characteristics. Conclusion. Surgical valve choice since the adoption of TAVR has changed, with less frequent use of smaller valves. Increases in mechanical valve usage are likely a reflection of changing patient population.
The Full m Index Sets of P2×Pn
Authors: Liu Zhizhong , Liu Jinmeng , Ji Yurong
Published: December 2023

Shiu and Kwong (2008) studied the full friendly index set of P2×Pn, which only addressed the cases where m=0 or 1. In this paper, we significantly extend their work by determining the full m index set MP2×Pn for all values of m. Our key approach is to utilize graph embedding and recursion methods to deduce MP2×Pn for general m. In particular, we embed small graphs like C4 and K2 into P2×Pn and apply recursive techniques to prove the main results. This work expands the scope of previous graph labeling studies and provides new insights into determining the full m index set of product graphs. Given the broad range of applications for labeled graphs, this research can potentially impact fields like coding theory, communication network design, and more.
Spatial Gene-Expression Profiling Unveils Immuno-oncogenic Programs of NF1-Associated Peripheral Nerve Sheath Tumor Progression
Authors: Mitchell Dana K. , Burgess Breanne , White Emily E. , Smith Abbi E. , Sierra Potchanant Elizabeth A. , Mang Henry , Hickey Brooke E. , Lu Qingbo , Qian Shaomin , Bessler Waylan , Li Xiaohong , Jiang Li , Brewster Kylee , Temm Constance , Horvai Andrew , Albright Eric A. , Fishel Melissa L. , Pratilas Christine A. , Angus Steven P. , Clapp D. Wade , Rhodes Steven D.
Published: December 2023

Purpose:

Plexiform neurofibromas (PNF) are benign peripheral nerve sheath tumors (PNST) associated with neurofibromatosis type 1 (NF1). Despite similar histologic appearance, these neoplasms exhibit diverse evolutionary trajectories, with a subset progressing to malignant peripheral nerve sheath tumor (MPNST), the leading cause of premature death in individuals with NF1. Malignant transformation of PNF often occurs through the development of atypical neurofibroma (ANF) precursor lesions characterized by distinct histopathologic features and CDKN2A copy-number loss. Although genomic studies have uncovered key driver events promoting tumor progression, the transcriptional changes preceding malignant transformation remain poorly defined.

Experimental Design:

Here we resolve gene-expression profiles in PNST across the neurofibroma-to-MPNST continuum in NF1 patients and mouse models, revealing early molecular features associated with neurofibroma evolution and transformation.

Results:

Our findings demonstrate that ANF exhibit enhanced signatures of antigen presentation and immune response, which are suppressed as malignant transformation ensues. MPNST further displayed deregulated survival and mitotic fidelity pathways, and targeting key mediators of these pathways, CENPF and BIRC5, disrupted the growth and viability of human MPNST cell lines and primary murine Nf1-Cdkn2a-mutant Schwann cell precursors. Finally, neurofibromas contiguous with MPNST manifested distinct alterations in core oncogenic and immune surveillance programs, suggesting that early molecular events driving disease progression may precede histopathologic evidence of malignancy.

Conclusions:

If validated prospectively in future studies, these signatures may serve as molecular diagnostic tools to augment conventional histopathologic diagnosis by identifying neurofibromas at high risk of undergoing malignant transformation, facilitating risk-adapted care.
TABLE 1 from FBXW7-loss Sensitizes Cells to ATR Inhibition Through Induced Mitotic Catastrophe
Authors: O'Brien Siobhan , Ubhi Tajinder , Wolf Lucie , Gandhi Krishna , Lin Sichun , Chaudary Naz , Dhani Neesha C. , Milosevic Michael , Brown Grant W. , Angers Stephane
Published: December 2023

Oligo list
Figure S4 from FBXW7-loss Sensitizes Cells to ATR Inhibition Through Induced Mitotic Catastrophe
Authors: O'Brien Siobhan , Ubhi Tajinder , Wolf Lucie , Gandhi Krishna , Lin Sichun , Chaudary Naz , Dhani Neesha C. , Milosevic Michael , Brown Grant W. , Angers Stephane
Published: December 2023

Supplementary figure S4 shows the validation of the AZD6738 chemogenomic screen and quantification of cell cycle assays following treatment with AZD6738
Arterial Stiffness and Incident Diabetes
Authors: Sung Ki-Chul
Published: December 2023

Diabetes may induce multiple organ damage; therefore, early detection of individuals at high-risk of incident diabetes is important for timely risk assessment and intervention. Arterial stiffness (AS) occurs as a result of functional and structural changes in the arterial wall. Growing body of evidence suggests that AS is a risk factor for incident diabetes. Although each study could use different indicators for AS (ex cf-PWV, baPWV, etc.), they came to similar conclusion that AS was associated with higher risk of incident diabetes. The underlying mechanisms for the relationship of AS with risk of diabetes remain to be elucidated, but there could be several potential mechanisms. Diabetes and AS are expected to share common risk factors and influence each other, but recent research showed some evidence that AS can directly increase the risk of diabetes. The link between AS and incident diabetes has important clinical implications. First, it suggests that AS might be a useful marker for identifying people at high risk for developing diabetes. Second, it suggests that reducing AS may prevent or delay the onset of diabetes. Early detection and possible slowing of the vascular stiffening process with pharmacological agents and lifestyle interventions may reduce associated risks for diabetes.
Analysis of Immune-Related Adverse Events of Atezolizumab and Bevacizumab in Patients with Hepatocellular Carcinoma: A Multicentre Cohort Study
Authors: Nam Heechul , Lee Jaejun , Han Ji Won , Lee Soon Kyu , Yang Hyun , Lee Hae Lim , Sung Pil Soo , Kim Hee Yeon , Kim Seok-Hwan , Song Myeong Jun , Kwon Jung-Hyun , Kim Chang Wook , Nam Soon Woo , Bae Si Hyun , Choi Jong Young , Yoon Seung Kew , Jang Jeong Won
Published: December 2023

Introduction: Despite the emergence of atezolizumab and bevacizumab (A + B) as standard first-line systemic therapy for unresectable hepatocellular carcinoma (HCC), a comprehensive understanding of the clinical significance of immune-related adverse events (irAEs) remains limited. We aimed to assess the impact of irAEs on patients with HCC undergoing A + B treatment. Methods: This multicentre retrospective study included consecutive patients with HCC who were treated with the A + B regimen from September 2020 to December 2022. Patients were categorized into three groups based on the severity of irAEs, ranging from those without any experience of irAEs to those with severe irAEs. Results: This study included 150 patients with HCC, with a mean age of 63.3 years. Among them, 93.3% of patients were classified as Barcelona Clinic Liver Cancer stage C, 52.0% had portal vein tumour thrombosis (PVTT), and 60.7% extrahepatic spread. Patients were classified as follows: group 1 (n = 84) had no irAEs, group 2 (n = 37) had mild irAEs (grade 1-2), and group 3 (n = 29) had severe irAEs (grade ≥3). The median overall survival (OS), progression-free survival (PFS), and time-to-treatment discontinuation (TTD) were 13.6, 5.7, and 3.6 months, respectively. Group 2 demonstrated significantly superior OS compared to group 1 (9.5 months) and group 3 (5.6 months), with a median OS of 23.0 months (p < 0.001). Furthermore, group 2 demonstrated significantly better outcomes in terms of PFS and TTD compared to both group 1 and group 3 (p < 0.001 for both). Multivariate analysis identified mild irAEs (hazard ratio [HR], 0.353; p = 0.010), ALBI grade 1 (HR, 0.389; p = 0.006), Child-Pugh class A (HR, 0.338; p = 0.002), and the absence of PVTT (HR, 0.556; p = 0.043) as independent predictors of better OS. Conclusion: Our study highlights the significant impact of irAE severity on the outcomes of patients with HCC receiving A + B. Notably, the occurrence of mild irAEs was independently associated with favourable survival, suggesting their potential role as surrogate indicators of HCC prognosis.
Exploring the Relationship between Lesion Morphology and Pathogenesis in Acute Small Subcortical Infarction
Authors: Huang Yen-Chu , Lee Jiann-Der , Lin Leng-Chieh , Weng Hsu-Huei , Yang Jen-Tsung , Tsai Yuan-Hsiung , Chen Chao-Hui
Published: December 2023

Introduction: Acute small subcortical infarctions (SSIs) result from occlusions of small penetrating arteries, and the underlying pathological factors can have different clinical implications. The objective of this study was to assess the clinical relevance of acute SSIs based on their sizes and morphologies. Methods: This retrospective case-control study analyzed clinical and imaging data of stroke patients with acute SSIs in penetrating artery territories who underwent magnetic resonance imaging within 5 days of stroke onset, registered between 2016 and 2020. We categorized these patients into three groups based on size and morphology: diameter <20 mm, diameter ≥20 mm, and separated lesions. We then evaluated their clinical characteristics and outcomes. Results: We analyzed 726 stroke patients with SSIs, among whom 573 had a diameter <20 mm, 99 had a diameter ≥20 mm, and 54 had separated lesions. The patients had a median age of 70 years and a median National Institutes of Health Stroke Scale (NIHSS) score of 4 on arrival. Patients who experienced early neurological deterioration (END) had a significantly lower chance of good functional outcomes (27.3% vs. 64.4%, p < 0.001). Patients with a diameter ≥20 mm had the most severe NIHSS on arrival and at day 3, the highest rate of END, and the lowest rate of good outcome at 3 months. The incidence of cardioembolism did not differ between patients with diameters of ≥20 mm and <20 mm. However, multiple logistic regression analysis revealed that separated lesions were more likely to be associated with cardioembolic stroke (adjusted odds ratio [aOR], 7.6; 95% confidence interval [CI], 2.0–28.5) and parent artery stenosis >50% (aOR, 3.8; 95% CI, 2.1–7.0) than a diameter of <20 mm. Moreover, SSIs with a diameter of ≥20 mm were found to be associated with an increased risk of END compared to those with a diameter of <20 mm (aOR, 2.9; 95% CI, 1.7–5.2). Conclusion: Our study suggests that the sizes and morphologies of acute SSIs may indicate different underlying pathologies and be linked to diverse clinical outcomes. Our findings also challenge the current imaging criteria for embolic stroke of undetermined source, as we did not find a link between large subcortical infarction and cardioembolic stroke.
Prevalence, Incidence, and Mortality of Multiple Sclerosis in Coimbra, Portugal
Authors: Correia Inês , Cunha Carolina , Bernardes Catarina , Nunes Carla , Macário Carmo , Sousa Lívia , Batista Sónia
Published: December 2023

Multiple sclerosis (MS) is the most common chronic inflammatory, demyelinating, and neurodegenerative disease of the central nervous system in young adults, representing the leading cause of nontraumatic disability in this population. The rising prevalence of MS worldwide makes it critical to recognize the absolute number of patients with MS, demanding the execution of a sustainable healthcare policy. In Portugal, only six studies evaluating MS rates were published, disclosing a prevalence of 64 cases per 100,000 persons and an incidence of 3.1 cases per 100,000 persons/year, but the mortality rates have not been reported. Thus, this observational, cross-sectional study aimed to assess MS prevalence, incidence, and mortality in the city of Coimbra, a region in the center of Portugal. Patients who fulfilled McDonald’s Diagnosis Criteria (2017) for MS were recruited. Inclusion criteria were defined according to prevalence, incidence, and mortality studies. The baseline demographic and clinical characterization of the prevalence study population was performed. The MS prevalence rate in Coimbra was 143.45 cases per 100,000 inhabitants. Between 2018 and 2021, the cumulative incidence was 8.52 new cases per 100,000 persons/year. The mortality rate between 2018 and 2021 was 2.84 deaths per 100,000 inhabitants. MS prevalence and incidence in Coimbra are higher than reported in previous similar studies and comparable to Europe’s mean prevalence and incidence.
Updating of higher education curriculum for future engineers during the COVID-19 pandemic
Authors: Galustyan Olga V. , Zhirkova Galina P. , Сan Wang , Gamisonia Saida S. , Boldyrev Igor I. , Khripunkova Olga V.
Published: December 2023

Higher education is immersed in unpredictable environments and is facing challenges during the Coronavirus Disease 2019 (COVID-19) pandemic. It needs to adapt to external changes constantly, especially to the level of development of science and technology as the most important component of education courses for future engineers are facing development difficulties within achieving their goals as the core of higher education. Curriculum serves as basis for realization of goals of higher education and curriculum for future engineers needs updating. The paper analyzes dilemma of updating of higher education curriculum for future engineers within its content and structure. During the learning process students participated in curriculum renewal and accelerated the upgrading of curriculum content and structure. Finishing the course, students conducted reflection, improved their understanding during the reflection process continuously that helped them to develop the habit of lifelong learning. The authors propose to expand teaching methods for the courses, to adapt engineering courses to the needs of economic development during the COVID-19 pandemic, to strengthen students’ interaction and participation, to supply multiple participation in curriculum “customization” countermeasures to update higher education curriculum for future engineers.
A review of the effects of active learning on high order thinking skills: a meta-analysis within islamic education
Authors: Karwadi Karwadi , Zakaria Abd Razak , Syafii Ahmad
Published: December 2023

This study aims to ascertain the impact of the Active learning method on high-order thinking skills (HOTS) within the realm of Islamic education. Our primary contribution is the comprehensive meta-analysis of various preliminary and university educational studies. Using RStudio, we analyzed the differences in effect sizes, variations, and groups among studies. The findings indicate that the Active learning method significantly enhances HOTS, with the mixed learning method showing the most pronounced effect. We adopted a systematic approach, examining diverse learning methods like genre-based learning and blended learning model. Our research design entailed a meticulous meta-analysis of pre-existing literature rather than primary experimental or survey-based methods. However, we identified high heterogeneity in effect sizes as a limitation, suggesting the need for more nuanced studies in varied contexts. This research underscores educators' need to adapt learning strategies suited for specific educational levels, pointing towards a brighter horizon for tailored pedagogical interventions.
Digital literacy practices of novice English as a foreign language teacher in writing research articles for publication
Authors: Deiniatur Much , Cahyono Bambang Yudi
Published: December 2023

Digital literacy is essential in writing research articles for publication in today's digital age, particularly for novice english as a foreign language (EFL) teacher trying to publish their research articles. This qualitative research explores the digital literacy practices of novice EFL teachers in writing research articles for publication, including the digital tools they use, their purposes for using these tools, and the challenges they face in using them. The data were collected using a questionnaire and interview. The study found that novice EFL teachers conceptualized digital literacy as the ability to search and evaluate credible online sources, using word processing and digital editing tools, collaborating online, and publishing their work digitally. Novice EFL teachers use various digital tools, such as word processing software, reference management software, and online academic databases, to improve their research and writing process. They use these tools for various purposes, such as collaborating with peers, improving their writing skills, and publishing their work online. However, novice EFL teachers face limited technical issues, limited access, inadequate technology infrastructure, and time management. It is recommended that academic institutions provide support to help novice EFL teachers develop their digital literacy skills, including technical support services, and training programs.
Teachers' experiences in sekolah penggerak program: a retrospective case study
Authors: Vebrianto Rian , Hermita Neni , Irawan Dedi , Mujtahid Iqbal Miftakhul , Thahir Musa
Published: December 2023

The Sekolah Penggerak program is one of the Indonesian Government's efforts to realize the vision of Indonesian education, namely an advanced Indonesia that is sovereign, independent, and possesses the Pancasila personality. As the leading actors in education, teachers play an important role in implementing educational programs. This study was carried out to examine the experiences of teachers involved in the Sekolah Penggerak program regarding the impact of implementing the program. This study is qualitative with an exploratory case study design and a retrospective approach. The participants in this study were 15 mover teachers willing to participate, selected using a purposive sampling technique. To collect data, an open-ended questionnaire, and semi-structured interviews were used. The results of the study reveal that, in general, the Sekolah Penggerak program has a positive impact on teachers, namely helping them change mindsets to be more innovative in utilizing student-focused learning, and on students, namely increasing their motivation and critical skills. The experiences after participating in the Sekolah Penggerak program also direct teachers to be involved in collaborative reflective practice of program implementation to produce teachers who are more professional so that this program runs more effectively in the future.
A viewpoint on folklore education: providing students freedom and empowerment
Authors: Agung Antonius Setyawan Sugeng Nur , Suryaman Maman , Sayuti Suminto A.
Published: December 2023

Oral folklore tradition is a unique phenomenon in West Borneo. This study aims to gain the lecturer's perspectives and reflection toward its implementation as a project-based activity for encouraging university students to transform local folklore into texts in English. It combines Finnegan's instructional procedure, and Gordon's synectic model and the creative state, which has been defined as creative instruction. Multiple observations and an in-depth interview with the folklore lecturer were conducted for this qualitative investigation. The lecturer is recognized as being exceptionally representative of this study employing purposive sampling under lived experience study because of his proficiency and enthusiasm. Having this creative instruction under supervision makes it clear that there is more room for the student's imagination and creativity to grow throughout this project-based activity. It gives them freedom to freely pursue their interests. Without excluding the possibilities of use in areas where there is still local folklore, this creative instruction is specifically suited for regions that are still rich in oral tradition. Further research is essential, nevertheless, as this study does not go into great detail on the perspectives and involvement among various students, the diversity of cultures and geographies, or the advancement of artificial intelligence (AI).
Novel differential power processing technique for uneven partial shading mitigation in PV systems
Authors: Murkute Subhash , Kulkarni (Deodhar) Vandana Abhay
Published: December 2023

Photovoltaic (PV) system output power greatly depends on environmental operating conditions. Partial shaded condition (PSC) operates PV string under mismatch. PV module mismatch has been one of the major causes for reduced amount of output power. Maximizing the amount of energy extraction from PV system under mismatch greatly influenced by conversion efficiency as well as the mismatch mitigation topology used. Differential power processing (DPP) is one of the advanced techniques to deal with mismatch conditions and enhance power output from a PV system. In this paper hybrid modular DPP topology is presented. The proposed technique mitigates the effect of mismatches at submodule and enhance power extraction from PV string. Since in majority shading on a PV module is nonuniform. The conversion efficiency of module level DPP shading mitigation techniques enhanced using submodule level DPP architecture. To demonstrate its applicability simulation study is carried out in MATLAB Simulink and results are compared with traditional bypass method and module level DPP. Simulation results showed the reduction in mismatch loss and improvement in efficiency and power output.