bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined molecular subtyping, grading, and segmentation of glioma using multi-task deep learning
Authors: van der Voort Sebastian R , Incekara Fatih , Wijnenga Maarten M J , Kapsas Georgios , Gahrmann Renske , Schouten Joost W , Nandoe Tewarie Rishi , Lycklama Geert J , De Witt Hamer Philip C , Eijgelaar Roelant S , French Pim J , Dubbink Hendrikus J , Vincent Arnaud J P E , Niessen Wiro J , van den Bent Martin J , Smits Marion , Klein Stefan
Published: July 2022

Background

Accurate characterization of glioma is crucial for clinical decision making. A delineation of the tumor is also desirable in the initial decision stages but is time-consuming. Previously, deep learning methods have been developed that can either non-invasively predict the genetic or histological features of glioma, or that can automatically delineate the tumor, but not both tasks at the same time. Here, we present our method that can predict the molecular subtype and grade, while simultaneously providing a delineation of the tumor.

Methods

We developed a single multi-task convolutional neural network that uses the full 3D, structural, preoperative MRI scans to predict the IDH mutation status, the 1p/19q co-deletion status, and the grade of a tumor, while simultaneously segmenting the tumor. We trained our method using a patient cohort containing 1508 glioma patients from 16 institutes. We tested our method on an independent dataset of 240 patients from 13 different institutes.

Results

In the independent test set, we achieved an IDH-AUC of 0.90, an 1p/19q co-deletion AUC of 0.85, and a grade AUC of 0.81 (grade II/III/IV). For the tumor delineation, we achieved a mean whole tumor Dice score of 0.84.

Conclusions

We developed a method that non-invasively predicts multiple, clinically relevant features of glioma. Evaluation in an independent dataset shows that the method achieves a high performance and that it generalizes well to the broader clinical population. This first-of-its-kind method opens the door to more generalizable, instead of hyper-specialized, AI methods.
Fastigial nuclei surgical damage and focal midbrain disruption implicate PAG survival circuits in cerebellar mutism syndrome
Authors: McAfee Samuel S , Zhang Silu , Zou Ping , Conklin Heather M , Raches Darcy , Robinson Giles , Gajjar Amar , Khan Raja , Klimo Paul , Patay Zoltan , Scoggins Matthew A
Published: July 2022

Background

Pediatric postoperative cerebellar mutism syndrome (CMS) is a rare but well-known complication of medulloblastoma (Mb) resection with devastating effects on expressive language, mobility, cognition, and emotional regulation that diminishes quality of life for many Mb survivors. The specific anatomical and neuronal basis of CMS remains obscure. We address this issue by identifying patterns of surgical damage and secondary axonal degeneration in Mb survivors with CMS.

Methods

Children with Mb deemed high risk for CMS based on intraventricular location of the tumor had T1 images analyzed for location(s) of surgical damage using a specially developed algorithm. We used three complementary methods of spatial analysis to identify surgical damage linked to CMS diagnosis. Magnetization transfer ratio (MTR) images were analyzed for evidence of demyelination in anatomic regions downstream of the cerebellum, indicating neuronal dysfunction.

Results

Spatial analyses highlighted damage to the fastigial nuclei and their associated cerebellar cortices as the strongest predictors of CMS. CMS-related MTR decrease was greatest in the ventral periaqueductal gray (PAG) area and highly consistent in the left red nucleus.

Conclusion

Our evidence points to disruption of output from the fastigial nuclei as a likely causal trigger for CMS. We propose that core CMS symptoms result from a disruption in the triggering of survival behaviors regulated by the PAG, including the gating of vocalization and volitional movement. The fastigial nuclei provide the densest output to the PAG from the cerebellum, thus sparing these structures may provide a greater likelihood of CMS prevention.
Decoupling engineering of formamidinium–cesium perovskites for efficient photovoltaics
Authors: Chen Haoran , Wang Yong , Fan Yingping , Chen Yuetian , Miao Yanfeng , Qin Zhixiao , Wang Xingtao , Liu Xiaomin , Zhu Kaicheng , Gao Feng , Zhao Yixin
Published: July 2022

Although pure formamidinium iodide perovskite (FAPbI3) possesses an optimal gap for photovoltaics, their poor phase stability limits the long-term operational stability of the devices. A promising approach to enhance their phase stability is to incorporate cesium into FAPbI3. However, state-of-the-art formamidinium–cesium (FA–Cs) iodide perovskites demonstrate much worse efficiency compared with FAPbI3, limited by the different crystallization dynamics of formamidinium and cesium, which result in poor composition homogeneity and high trap densities. We develop a novel strategy of crystallization decoupling processes of formamidinium and cesium via a sequential cesium incorporation approach. As such, we obtain highly reproducible, highly efficient and stable solar cells based on FA1–xCsxPbI3 (x = 0.05–0.16) films with uniform composition distribution in the nanoscale and low defect densities. We also revealed a new stabilization mechanism for Cs doping to stabilize FAPbI3, i.e. the incorporation of Cs into FAPbI3 significantly reduces the electron–phonon coupling strength to suppress ionic migration, thereby improving the stability of FA–Cs-based devices.
When feelings hurt: Learning how to talk with families about the role of emotions in physical symptoms
Authors: Boerner Katelynn E , Dhariwal Amrit K , Chapman Andrea , Oberlander Tim F
Published: July 2022

Emotions are at the core of all human experiences, but talking about emotions is challenging, particularly in the context of medical encounters focused on somatic symptoms. Transparent, normalizing, and validating communication about the mind-body connection opens the door for respectful, open dialogue between the family and members of the care team, acknowledging the lived experience that is brought to the table in understanding the problem and co-creating a solution.
Signal amplification of araC pBAD using a standardized translation initiation region
Authors: Shilling Patrick J , Khananisho Diana , Cumming Alister J , Söderström Bill , Daley Daniel O
Published: July 2022

araC pBAD is a genetic fragment that regulates the expression of the araBAD operon in bacteria, which is required for the metabolism of L-arabinose. It is widely used in bioengineering applications because it can drive regulatable and titratable expression of genes and genetic pathways in microbial cell factories. A notable limitation of araC pBAD is that it generates a low signal when induced with high concentrations of L-arabinose (the maximum ON state). Herein we have amplified the maximum ON state of araC pBAD by coupling it to a synthetically evolved translation initiation region (TIREVOL). The coupling maintains regulatable and titratable expression from araC pBAD and yet increases the maximal ON state by >5-fold. The general principle demonstrated in the study can be applied to amplify the signal from similar genetic modules.

Graphical Abstract
Interactions Among Heterodera glycines, Macrophomina phaseolina, and Soybean Genotype
Authors: Lopez-Nicora Horacio D. , Ralston Timothy I. , Diers Brian W. , Dorrance Anne E. , Niblack Terry L.
Published: July 2022

Heterodera glycines, the soybean cyst nematode (SCN), and fungal pathogen Macrophomina phaseolina are economically important soybean pathogens that may coinfest fields. Resistance remains the most effective management tactic for SCN, and the rhg1-b resistance allele derived from plant introduction 88788 is most commonly deployed in the northern United States. The concomitant effects of SCN and M. phaseolina on soybean performance, as well as the effect of the rhg1-b allele in two different genetic backgrounds, were evaluated in three environments (during 2013 to 2015) and a greenhouse bioassay. Within two soybean populations, half of the lines had the rhg1-b allele, and the other half had the susceptible allele in the backgrounds of the cultivars IA3023 and LD00-3309. Significant interactions between soybean rhg1-b allele and M. phaseolina-infested plots were observed in 2014. In all experiments, initial SCN populations (Pi) and M. phaseolina in roots were associated with reduced soybean yield. SCN reproduction factor (RF = final population/Pi) was affected by SCN Pi, rhg1-b, and genetic background. A background-by-genotype interaction on yield was observed only in 2015, with a stronger rhg1-b effect in the LD00-3309 background, which suggested that the susceptible parent ‘IA3023’ is tolerant to SCN. SCN female index from greenhouse experiments was compared with field RF, and Lin’s concordance and Pearson’s correlation coefficients decreased with increasing field SCN Pi in soil. In this study, both SCN and M. phaseolina reduced soybean yield asymptomatically, and the impact of SCN rhg1-b resistance was dependent on SCN virulence but also population density.
Novel anesthetics in pediatric practice: is it time?
Authors: Useinovic Nemanja , Jevtovic-Todorovic Vesna
Published: July 2022

Purpose of review

Steadily mounting evidence of anesthesia-induced developmental neurotoxicity has been a challenge in pediatric anesthesiology. Considering that presently used anesthetics have, in different animal models, been shown to cause lasting behavioral impairments when administered at the peak of brain development, the nagging question, ‘Is it time for the development of a new anesthetic’ must be pondered.

Recent findings

The emerging ‘soft analogs’ of intravenous anesthetics aim to overcome the shortcomings of currently available clinical drugs. Remimazolam, a novel ester-analog of midazolam, is a well tolerated intravenous drug with beneficial pharmacological properties. Two novel etomidate analogs currently in development are causing less adrenocortical suppression while maintaining equally favorable hemodynamic stability and rapid metabolism. Quaternary lidocaine derivatives are explored as more potent and longer lasting alternatives to currently available local anesthetics. Xenon, a noble gas with anesthetic properties, is being considered as an anesthetic-sparing adjuvant in pediatric population. Finally, alphaxalone is being reevaluated in a new drug formulation because of its favorable pharmacological properties.

Although a number of exciting anesthetic drugs are under development, there is currently no clear evidence to suggest their lack of neurotoxic properties in young brain. Well designed preclinical studies are needed to evaluate their neurotoxic potential.
Prevention of pulmonary complications in sedated patients undergoing interventional procedures in the nonoperating room anesthesia setting
Authors: Urdaneta Felipe , Wardhan Richa , Wells Gregory , White Jeffrey D.
Published: July 2022

Purpose of review

Nonoperating room anesthesia (NORA) procedures have expanded in number, variety, and complexity. NORA involves all age groups, including frail older adults and patients often considered too sick to tolerate traditional surgical interventions. Postoperative pulmonary complications are a significant source of adverse events in the perioperative setting. We present a review focused on preventing pulmonary complications in the interventional NORA setting.

Recent findings

NORA locations should function as independent, autonomous ambulatory units. We discuss a strategic plan involving a thorough preoperative evaluation of patients, including recognizing high-risk patients and their anesthetic management. Finally, we offer guidance on the challenges of conducting sedation and anesthesia in patients with coronavirus disease 2019 (COVID-19) or a history of COVID-19.

The demands on the interventional NORA anesthesia team are increasing. Strategic planning, checklists, consistent staffing assignments, and scheduled safety drills are valuable tools to improve patient safety. In addition, through quality improvement initiatives and reporting, NORA anesthetists can achieve reductions in periprocedural pulmonary complications.
Regional anesthesia techniques for cardiac surgery: where are we?
Authors: Kim Rosa S. , Gonzalez-Ciccarelli Luis F. , Brovman Ethan Y.
Published: July 2022

Purpose of review

Inadequate pain relief after cardiac surgery results in decreased patient experience and satisfaction, increased opioid consumption with its associated adverse consequences, and reduced efficiency metrics. To mitigate this, regional analgesic techniques are an increasingly important part of the perioperative cardiac anesthesia care plan. The purpose of this review is to compare current regional anesthesia techniques, and the relative evidence supporting their efficacy and safety in cardiac surgery.

Recent findings

Numerous novel plane blocks have been developed in recent years, with evidence of improved pain control after cardiac surgery.

The current data supports the use of a variety of different regional anesthesia techniques to reduce acute pain after cardiac surgery. However, future randomized trials are needed to quantify and compare the efficacy and safety of different regional techniques for pain control after cardiac surgery.
Biologic disease-modifying antirheumatic drugs to treat multisystem inflammatory syndrome in children
Authors: Cron Randy Q.
Published: July 2022

Purpose of review

Multisystem inflammatory syndrome in children (MIS-C) is a postinfectious complication of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection primarily affecting children. MIS-C shares features with Kawasaki disease (KD) and cytokine storm syndrome (CSS) frequently requiring intensive care support. Although intravenous immunoglobulin (IVIg) and glucocorticoids (GCs) are effective therapeutics for most, refractory MIS-C is treated with various biologic disease-modifying antirheumatic drugs (bDMARDs). Understanding the clinical features, inflammatory cytokines, and genetic associations provides rationale for bDMARD in treating severe MIS-C.

Recent findings

Children with MIS-C have clinical KD features and often present in hypovolemic and cardiogenic shock requiring volume repletion (gastrointestinaI losses) and cardiac pressor support (epinephrine). Investigation of MIS-C serum reveals elevated pro-inflammatory cytokines [interleukin (IL)-1, IL-6, IL-18, interferon gamma (IFNγ), tumor necrosis factor (TNF)], but to a lesser extent than other established CSS. Gene sequencing of MIS-C children identifies heterozygous mutations in CSS associated genes. Treatment of refractory (IVIg and GC) MIS-C with bDMARDs to IL-1, IL-6, and TNF is efficacious for survival as well as resolving cardiac and coronary artery inflammation.

MIS-C is a postinfectious complication of SARS-CoV-2 resembling KD and CSS, both genetically and by pro-inflammatory cytokines. MIS-C that is refractory to IVIg and GC is routinely responsive to bDMARDs targeting IL-1, IL-6, and TNF.
Challenges of caring for transgender and gender diverse patients with rheumatic disease: presentation of seven patients and review of the literature
Authors: Mathias Kristen , Mathias Lauren , Amarnani Abhimanyu , Samko Tracey , Lahita Robert G. , Panush Richard S.
Published: July 2022

Purpose of review

As perspectives on sex and gender identity have evolved, there has been an increase in the practice of transgender medicine. Within rheumatology, however, there is a dearth of information about rheumatic disease in transgender and gender diverse (TGGD) individuals. This is important, as sex hormones affect the etiopathogenesis and expression of autoimmune diseases. We therefore sought to identify TGGD patients with rheumatic disease, review their clinical courses, and appraise existing literature about this population.

Recent findings

Of 1053 patients seen at the Los Angeles County and University of Southern California Medical Center from 2019 through 2021, five transgender men and two transgender women with rheumatic disease were identified. Most patients’ disease courses were not overtly impacted by gender affirming hormone therapy (GAHT). Six of seven patients had psychosocial barriers to care. Our systematic review found 11 studies with 11 transgender women and two transgender men. In 12 of 13 patients, GAHT possibly modulated the patients’ rheumatic disease.

Our observations suggest GAHT need not be a strict contraindication in TGGD patients with rheumatic disease. TGGD patients often face significant psychosocial barriers. Additional information about this population and empathy toward their health disparities are needed.
A Complement Type to SRS-Schwab Adult Spinal Deformity Classification: The Failure of Pelvic Compensation
Authors: Kwon Ohsang , Lee Sanghoon , Park Sang-Min , Yeom Jin S. , Kim Ho-Joong
Published: July 2022

Study Design.

Retrospective review.

Objective.

To determine characteristics of patients with adult spinal deformity (ASD) who showed failed pelvic compensation even with significant sagittal imbalance.

Background.

Patients who show failed pelvic compensation despite significant sagittal imbalance reportedly present distinct clinical outcomes. However, to our knowledge, no study has clearly defined or characterized this subgroup of patients with ASD.

Materials and Methods.

We examined 126 patients who underwent reconstructive spinal surgery for ASD between September 2016 and September 2020. Radiographic spinopelvic parameters were assessed. The patients were divided into four quadrant groups based on the two axes of pelvic tilt/pelvic incidence (PT/PI) and the sagittal vertical axis (SVA) with reference to the population median values (0.68 and 147.5 mm, respectively). Patients with low PT/PI and high SVA were considered to have failed pelvic compensation, and they were compared with other patient groups.

Results.

Patients with failed pelvic compensation (low PT/PI and high SVA) had worse clinical outcomes than those with successful pelvic compensation (high PT/PI and high SVA) at one year after surgery. Regarding radiographic outcomes, patients with failed pelvic compensation showed a significantly larger postoperative SVA even after correcting the PI−lumbar lordosis mismatch was corrected to a comparable range with the group of successful pelvic compensation. Notably, patients with failed pelvic compensation showed larger cross-sectional areas of the psoas and back extensor muscles than those with successful pelvic compensation. This suggests that failure of pelvic compensation did not occur because of back muscle weakness, which implies another underlying pathophysiology, including neurological origin.

Conclusion.

Compared with patients with successful pelvic compensation, those with failed pelvic compensation showed lower postoperative improvements in clinical and radiographic outcomes. Therefore, it is important to consider pelvic compensation when planning surgical correction of deformities. Distinct surgical approaches, including overcorrection of the PI−lumbar lordosis mismatch or global sagittal alignment, should be attempted to ensure postoperative symptom improvement.
Chemokines in ICU Delirium: An Exploratory Study
Authors: Smith Ryan J. , Rabinstein Alejandro A. , Cartin-Ceba Rodrigo , Singh Vijay P. , Lachner Christian , Khatua Biswajit , Trivedi Shubham , Gajic Ognjen
Published: July 2022

OBJECTIVES:

The pathophysiology of delirium is complex and incompletely understood. Inflammation is hypothesized to be integral to its development due to effects on blood brain barrier integrity, facilitation of leukocyte extravasation into brain parenchyma, and propagation of neuroinflammation. Septic shock is the prototypical condition associated with ICU delirium; however, the relative contribution of resultant hypotension and systemic inflammation to the development of delirium is unknown.

DESIGN:

This was a prospective exploratory study.

SETTING:

A multidisciplinary ICU at an academic medical center in Phoenix, AZ.

PATIENTS:

Critically ill patients older than or equal to 18 years old admitted to the ICU.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Screening for delirium was performed using the Confusion Assessment Method for the ICU tool. The levels of C-C motif ligand 2 (CCL2), C-C motif ligand 3, C-X-C motif chemokine ligand 1, C-X-C motif chemokine ligand 10, and interleukin-8 were measured in serum samples obtained within 12 hours of ICU admission. Univariate and multivariate analyses were performed to assess the association of delirium with patient data pertaining to hospital course, laboratory values, vital signs, medication administration, and levels of the aforementioned chemokines. Forty-one of 119 patients (34.5%) in the study cohort developed ICU delirium. Each chemokine studied was associated with delirium on univariate analyses; however, CCL2 was the only chemokine found to be independently associated with the development of delirium on multivariable analysis. The association of increased CCL2 levels with delirium remained robust in various models controlling for age, presence of shock, Sequential Organ Failure Assessment score, Acute Physiology and Chronic Health Evaluation IV score, mean arterial pressure at presentation, lowest mean arterial pressure, and total opioid, midazolam, propofol, and dexmedetomidine exposure.

CONCLUSIONS:

The demonstrated relationship between CCL2 and delirium suggests this chemokine may play a role in the development of delirium and warrants further investigation.
Targeting the DNA damage response beyond poly(ADP-ribose) polymerase inhibitors: novel agents and rational combinations
Authors: Ngoi Natalie Y.L. , Westin Shannon N. , Yap Timothy A.
Published: July 2022

Purpose of review

Poly(ADP-ribose) polymerase (PARP) inhibitors have transformed treatment paradigms in multiple cancer types defined by homologous recombination deficiency (HRD) and have become the archetypal example of synthetic lethal targeting within the DNA damage response (DDR). Despite this success, primary and acquired resistance to PARP inhibition inevitability threaten the efficacy and durability of response to these drugs. Beyond PARP inhibitors, recent advances in large-scale functional genomic screens have led to the identification of a steadily growing list of genetic dependencies across the DDR landscape. This has led to a wide array of novel synthetic lethal targets and corresponding inhibitors, which hold promise to widen the application of DDR inhibitors beyond HRD and potentially address PARP inhibitor resistance.

Recent findings

In this review, we describe key synthetic lethal interactions that have been identified across the DDR landscape, summarize the early phase clinical development of the most promising DDR inhibitors, and highlight relevant combinations of DDR inhibitors with chemotherapy and other novel cancer therapies, which are anticipated to make an impact in rationally selected patient populations.

The DDR landscape holds multiple opportunities for synthetic lethal targeting with multiple novel DDR inhibitors being evaluated on early phase clinical trials. Key challenges remain in optimizing the therapeutic window of ATR and WEE1 inhibitors as monotherapy and in combination approaches.
Targeting the methionine−methionine adenosyl transferase 2A−S-adenosyl methionine axis for cancer therapy
Authors: Guo Jiamin , Yang Yanzhong , Buettner Ralf , Rosen Steven T.
Published: July 2022

Purpose of review

In this review, we summarize the biological roles of methionine, methionine adenosyl transferase 2A (MAT2A) and S-adenosyl methionine (SAM) in methylation reactions during tumorigenesis. Newly emerged inhibitors targeting the methionine−MAT2A−SAM axis will be discussed.

Recent findings

SAM is the critical and global methyl-donor for methylation reactions regulating gene expression, and in mammalian cells, it is synthesized by MAT2A using methionine. Recent studies have validated methionine and MAT2A as metabolic dependencies of cancer cells because of their essential roles in SAM biosynthesis. MAT2A inhibition leads to synthetic lethality in methylthioadenosine-phosphorylase (MTAP)-deleted cancers, which accounts for 15% of all cancer types. Of note, remarkable progress has been made in developing inhibitors targeting the methionine−MAT2A−SAM axis, as the first-in-class MAT2A inhibitors AG-270 and IDE397 enter clinical trials to treat cancer.

The methionine−MAT2A−SAM axis plays an important role in tumorigenesis by providing SAM as a critical substrate for abnormal protein as well as DNA and RNA methylation in cancer cells. Targeting SAM biosynthesis through MAT2A inhibition has emerged as a novel and promising strategy for cancer therapy.
Actual impact of angiotensin II receptor blocker or calcium channel blocker monotherapy on renal function in real-world patients
Authors: Satoh Michihiro , Hirose Takuo , Satoh Hironori , Nakayama Shingo , Obara Taku , Murakami Takahisa , Muroya Tomoko , Asayama Kei , Kikuya Masahiro , Mori Takefumi , Imai Yutaka , Ohkubo Takayoshi , Metoki Hirohito
Published: July 2022

Objective:

This observational retrospective cohort study investigates the effect of antihypertensive therapy with angiotensin II receptor blockers (ARBs) or dihydropyridine calcium channel blockers (dCCBs) monotherapy on renal function using longitudinal real-world health data of a drug-naive, hypertensive population without kidney disease.

Methods:

Using propensity score matching, we selected untreated hypertensive participants (n = 10 151) and dCCB (n = 5078) or ARB (n = 5073) new-users based on annual health check-ups and claims between 2008 and 2020. Participants were divided by the first prescribed drug.

Results:

The mean age was 51 years, 79% were men and the mean estimated glomerular filtration rate (eGFR) was 78 ml/min per 1.73 m2. Blood pressure rapidly decreased by approximately 10% in both treatment groups. At the 1-year visit, eGFR levels decreased in the ARB group by nearly 2% but increased in the dCCB group by less than 1%. However, no significant difference was apparent in the annual eGFR change after the 1-year visit. The risk for composite kidney outcome (new-onset proteinuria or eGFR decline ≥30%) was lowest in the ARB group owing to their robust effect on preventing proteinuria: hazard ratio (95% confidence interval) for proteinuria was 0.91 (0.78–1.05) for the dCCB group and 0.54 (0.44–0.65) for the ARB group, compared with that for the untreated group after ending follow-up at the last visit before changing antihypertensive treatment.

Conclusion:

From the present findings based on the real-world data, ARBs can be recommended for kidney protection even in a primary care setting. Meanwhile, dCCB treatment initially increases eGFR with no adverse effects on proteinuria.
Elevated blood pressure in pregnant women with gestational diabetes according to the WHO criteria: importance of overweight
Authors: Birukov Anna , Glintborg Dorte , Schulze Matthias B. , Jensen Tina K. , Kuxhaus Olga , Andersen Louise B. , Kräker Kristin , Polemiti Elli , Jensen Boye L. , Jørgensen Jan S. , Dechend Ralf , Andersen Marianne S.
Published: July 2022

Objective:

Hypertension before and during early pregnancy has been associated with an increased risk of gestational diabetes mellitus (GDM) in retrospective analyses. We aimed to investigate the prospective blood pressure trackings in a population-based cohort of pregnant women, who were stratified according to their metabolic status in early third trimester.

Methods:

We recorded blood pressure longitudinally during pregnancy in 1230 women from the Odense Child Cohort, Denmark. Fasting glucose and insulin were measured at gestational weeks 28–30. Metabolic status was evaluated according to the WHO 2013 threshold for GDM (GDM-WHO: fasting plasma glucose ≥5.1 mmol/l), insulin and homeostatic model assessment of insulin resistance (HOMA-IR). Relationships between metabolic status in third trimester and blood pressure trajectories were evaluated with adjusted linear mixed models. Trajectory was defined as blood pressure records in pregnancy per 4 weeks interval.

Results:

Prevalence of GDM-WHO was 40% (498/1230). GDM-WHO was associated with 1.46 (0.22–2.70) mmHg higher SBP and 1.04 (0.07–2.01) mmHg higher DBP trajectories in the overall cohort. The associations were driven by differences in the overweight group, with 3.14 (1.05–5.25) mmHg higher SBP and 1.94 (0.42–3.47) mmHg higher DBP per 4 weeks in women with GDM-WHO compared with women without GDM-WHO. GDM-WHO was not associated with blood pressure in women with normal weight. Blood pressure trajectories were elevated across quartiles of insulin resistance.

Conclusion:

GDM-WHO is associated with higher blood pressure in pregnancy, and there appears to be a stronger effect in overweight women.
In Vitro Expansion of Corneal Endothelial Cells for Clinical Application: Current Update
Authors: Hazra Swatilekha , Sneha Iskala V. , Chaurasia Sunita , Ramachandran Charanya
Published: July 2022

Endothelial dysfunction is one of the leading causes of corneal blindness and one of the common indications for keratoplasty. At present, the standard of treatment involves the replacement of the dysfunctional endothelium with healthy tissue taken from a donor. Because there is a paucity of healthy donor tissues, research on the corneal endothelium has focused primarily on expanding these cells in the laboratory for transplantation in an attempt to reduce the gap between the demand and supply of donor tissues for transplantation. To expand these cells, which are nonmitotic in vivo, various mitogens, substrates, culture systems, and alternate strategies have been tested with varying success. The biggest challenge has been the limited proliferative capacity of these cells compounded with endothelial to mesenchymal transition that alters the functioning of these cells and renders them unsuitable for human transplantation. This review aims to give a comprehensive overview of the most common and successful techniques used in the culture of the cells, the current available evidence in support of epithelial to mesenchymal transition (EMT), alternate sources for deriving the corneal endothelial cells, and advances made in transplantation of these cells.
Increased expression of serum MCP-1, CCL3, IL-6, and IL-17 in patients with vitiligo and IL-17 as a potential clinical marker for active vitiligo
Authors: Zhao Xiaoling , Li Yalan , Li Zihan , Zhang Xiaochong , An Lihui , Sun Yujiao , Liu Dengxiang , Cheng Fang
Published: July 2022

Objective:

The purpose of this study was to find potential active markers in the progression of vitiligo.

Methods:

We compared 30 healthy controls to 60 patients with vitiligo (30 with active disease and 30 with stable disease) regarding the expression of serum MCP-1, CCL3, CCL5, CCL21, IL-6, and IL-17. Specimens were collected from May 2017 to December 2018. Serological detection was carried out by enzyme-linked immunosorbent assay.

Results:

We found that the serum levels of MCP-1, CCL3, IL-6, and IL-17 were significantly higher in patients with vitiligo than in healthy controls (P < 0.01) and that IL-17 was higher in patients with active vitiligo than in those with stable vitiligo (P < 0.01). After 3 months of treatment, the serum IL-17 level of patients with active vitiligo was not significantly different from that before treatment (P > 0.05); after 6 months of treatment, however, the serum IL-17 level had significantly decreased (P < 0.01).

Conclusions:

These findings suggest that the serum IL-17 level can be used as a marker of vitiligo disease activity, giving it certain guiding significance for clinical treatment.
A novel frameshift CYLD mutation in a family with multiple familial trichoepithelioma
Authors: Yang He-Dan , Wang Xiao-Po
Published: July 2022

Introduction:

Multiple familial trichoepithelioma is a rare autosomal dominant genodermatosis caused by a mutation in the CYLD gene. This disease is characterized by the development of multiple skin-colored papules and nodules mainly on the central face. We herein describe a family with multiple familial trichoepithelioma with a novel frameshift mutation in CYLD.

Case presentation:

The proband was an 8-year-old girl who presented with a 2-year history of numerous progressive, asymptomatic, firm skin-colored papules on her nasal dorsum, nasolabial folds, and eyelids. Histopathological examination was compatible with the typical findings of trichoepithelioma. Her father displayed similar but inconspicuous smaller lesions on the face. Mutation analysis of the proband identified a heterozygous frameshift mutation c.1181_1182insCTTTGAC (p.D394fs) in exon 10 of CYLD. This mutation was also detected in the proband’s father, but not in either her mother or 100 unrelated control individuals

Discussion:

There is no obvious genotype–phenotype correlation in patients with multiple familial trichoepithelioma. In our study, the girl had a severe clinical appearance characterized by facial disfiguration, whereas her father had inconspicuous smaller lesions despite having the same mutation. We also identified a novel frameshift mutation c.1181_1182insCTTTGAC (p.D394fs) in exon 10 of the CYLD gene. The presence of this mutation leads to premature translation termination and thus to the synthesis of a truncated protein.

Conclusion:

We found a novel frameshift mutation of the CYLD gene in a Chinese family, thus expanding the database of CYLD gene mutations in multiple familial trichoepithelioma.
Lipidomics in nutrition research
Authors: Castro-Alves Victor , Orešič Matej , Hyötyläinen Tuulia
Published: July 2022

Purpose of review

This review focuses on the recent findings from lipidomics studies as related to nutrition and health research.

Recent findings

Several lipidomics studies have investigated malnutrition, including both under- and overnutrition. Focus has been both on the early-life nutrition as well as on the impact of overfeeding later in life. Multiple studies have investigated the impact of different macronutrients in lipidome on human health, demonstrating that overfeeding with saturated fat is metabolically more harmful than overfeeding with polyunsaturated fat or carbohydrate-rich food. Diet rich in saturated fat increases the lipotoxic lipids, such as ceramides and saturated fatty-acyl-containing triacylglycerols, increasing also the low-density lipoprotein aggregation rate. In contrast, diet rich in polyunsaturated fatty acids, such as n-3 fatty acids, decreases the triacylglycerol levels, although some individuals are poor responders to n-3 supplementation.

The results highlight the benefits of lipidomics in clinical nutrition research, also providing an opportunity for personalized nutrition. An area of increasing interest is the interplay of diet, gut microbiome, and metabolome, and how they together impact individuals’ responses to nutritional challenges.
No time to die? Intrinsic apoptosis signaling in hematopoietic stem and progenitor cells and therapeutic implications
Authors: Hagenbourger Florian , Bohler Sheila , Erlacher Miriam
Published: July 2022

Purpose of review

Dysregulated apoptosis contributes to the pathogenesis of many hematologic malignancies. BH3-mimetics, antagonists of antiapoptotic BCL-2 proteins, represent novel, and promising cancer drugs. While the acute myelosuppressive effects of Venetoclax, the first Food and Drug Administration approved BCL-2 inhibitor, are fairly well described, little is known about side effects of novel BH3-mimetics and effects of chronic Venetoclax treatment.

Recent findings

Highly relevant publications focused on the effects of acute and chronic Venetoclax therapy, with focus on cell-type specific adaptive mechanisms, the emergence of clonal hematopoiesis, and the selection of BAX-mutated hematopoietic cells in patients treated with Venetoclax for a long period. Important advances were made in understanding primary and secondary Venetoclax resistance and prediction of Venetoclax response. Combination therapies of BH3-mimetics targeting different BCL-2 proteins are highly anticipated. However, human stem and progenitors require both MCL-1 and BCL-XL for survival, and serious myelosuppressive effects of combined MCL-1/BCL-XL inhibition can be expected.

Long-term studies are indispensable to profile the chronic side effects of Venetoclax and novel BH3-mimetics and better balance their risk vs. benefit in cancer therapy. Combination therapies will be powerful, but potentially limited by severe myelosuppression. For precision medicine, a better knowledge of BCL-2 proteins in the healthy and diseased hematopoietic system is required.
The new metabolic needs of hematopoietic stem cells
Authors: Bartram James , Filippi Marie-Dominique
Published: July 2022

Purpose of review

Hematopoietic stem cells (HSCs) are endowed with high regenerative potential to supply mature blood cells throughout life, under steady state or stress conditions. HSCs are thought to rely on glycolysis when in a quiescent state and to switch to oxidative phosphorylation to meet their metabolic needs during activation. Recently, a series of important studies reveals a higher degree of complexity that goes well beyond the dichotomy between glycolysis and oxidative phosphorylation. The purpose of this review is to summarize the recent findings highlighting the multifaceted metabolic requirements of HSC homeostasis.

Recent findings

Emerging evidence points to the importance of lysosomal catabolic activity and noncanonical retinoic acid pathway in maintaining HSC quiescence and stemness. HSC activation into cycle seems to be accompanied by a switch to glycolysis-mitochondrial coupling and to anabolic pathways, including Myc, aspartate-mediated purine synthesis.

Knowledge of metabolism of HSCs has dramatically increased in the past 2 years and reveals unexpected needs of HSCs during both their quiescent and activated state. Understanding how HSCs use metabolism for their functions will offer new opportunity for HSC-based therapies.
Connecting tremors – a circuits perspective
Authors: Buijink Arthur W.G. , van Rootselaar Anne-Fleur , Helmich Rick C.
Published: July 2022

Purpose of review

Tremor is one of the most prevalent movement disorders in clinical practice. Here, we review new insights in the pathophysiology of tremor. We focus on the three most common tremor disorders: essential tremor (ET), dystonic tremor syndrome (DTS), and Parkinson's disease (PD) tremor.

Recent findings

Converging evidence suggests that ET, DTS, and PD tremor are all associated with (partly) overlapping cerebral networks involving the basal ganglia and cerebello-thalamo-cortical circuit. Recent studies have assessed the role of these networks in tremor by measuring tremor-related activity and connectivity with electrophysiology and neuroimaging, and by perturbing network components using invasive and noninvasive brain stimulation. The cerebellum plays a more dominant and causal role in action tremors than in rest tremor, as exemplified by recent findings in ET, DTS, and re-emergent tremor in PD. Furthermore, the role of the cerebellum in DTS is related to clinical differences between patients, for example, whether or not the tremor occurs in a dystonic limb, and whether the tremor is jerky or sinusoidal.

Insight into the pathophysiological mechanisms of tremor may provide a more direct window into mechanism-based treatment options than either the etiology or the clinical phenotype of a tremor syndrome.
Deep brain stimulation in dystonia: factors contributing to variability in outcome in short and long term follow-up
Authors: Tisch Stephen
Published: July 2022

Purpose of review

Deep brain stimulation (DBS) is currently the most effective treatment for medically refractory dystonia with globus pallidus internus (GPi) usually the preferred target. Despite the overall success of DBS in dystonia, there remains variability in treatment outcome in both short and long-term follow-up, due to various factors. Factors contributing to variability in outcome comprise ’Dystonia Related’ including dystonia classification, semiology, duration, body distribution, orthopaedic deformity, aetiology and genetic cause. The majority of these factors are identifiable from clinical assessment, brain MRI and genetic testing, and therefore merit careful preoperative consideration. ’DBS related’ factors include brain target, accuracy of lead placement, stimulation parameters, time allowed for response, neurostimulation technology employed and DBS induced side-effects. In this review, factors contributing to variability in short and long-term dystonia DBS outcome are reviewed and discussed.

Recent findings

The recognition of differential DBS benefit in monogenic dystonia, increasing experience with subthalamic nucleus (STN) DBS and in DBS for Meige syndrome, elucidation of DBS side effects and novel neurophysiological and imaging techniques to assist in predicting clinical outcome.

Improved understanding of factors contributing to variability of DBS outcome in dystonia may assist in patient selection and predicting surgical outcomes.
Role of Error Catastrophe in Transmission Ability of Virus
Authors: Takahata Naoyuki , Sugawara Hirotaka
Published: July 2022

The role played by “error catastrophe” is explicitly taken into account in the mathematical formulation to analyze the COVID-19 data. The idea is to combine the mathematical genetics formalism of the error catastrophe of mutations in the virus gene loci with the standard model of epidemics which lacks the explicit incorporation of the mutation effect on the spreading of the viruses. We apply the formalism to the case of SARS-CoV-2 virus. We assume the “universality” of the error catastrophe in the process of analyzing the data. This means that some basic parameter to describe the error catastrophe is independent of which group (country or city) we deal with. Concretely, we analyze the omicron data of South Africa and then analyze the cases of Japan using the same value of the basic parameter derived in the South Africa analysis. The result of the excellent fittings of the two data, one from South Africa and the other from Japan with the common values of genetic parameters, justifies our universality assumption of these parameters.
Dislocation substructures in pure aluminium after creep deformation as studied by electron backscatter diffraction
Authors: Serrano-Munoz Itziar , Fernández Ricardo , Saliwan-Neumann Romeo , González-Doncel Gaspar , Bruno Giovanni
Published: July 2022

In the present work, electron backscatter diffraction was used to determine the microscopic dislocation structures generated during creep (with tests interrupted at the steady state) in pure 99.8% aluminium. This material was investigated at two different stress levels, corresponding to the power-law and power-law breakdown regimes. The results show that the formation of subgrain cellular structures occurs independently of the crystallographic orientation. However, the density of these cellular structures strongly depends on the grain crystallographic orientation with respect to the tensile axis direction, with 〈111〉 grains exhibiting the highest densities at both stress levels. It is proposed that this behaviour is due to the influence of intergranular stresses, which is different in 〈111〉 and 〈001〉 grains.
The effect of mobile device usage on creating text reviews
Authors: Park Keeyeon , Kim Hye-Jin , Kim Jong Min
Published: July 2022

Purpose

The purpose of this study is to examine how the usage of mobile devices influences text-posting behavior in the online review-generation process. This study attempts to improve the understanding of the negative impacts of mobile channels on the quality of online reviews.

Design/methodology/approach

The authors develop a series of hypotheses to investigate the text-posting behaviors with mobile device usage. To examine the authors' hypotheses, the authors collect online reviews posted in London hotels on Booking.com. The authors first use a logistic regression model to examine the relationship between the usage of mobile devices and text-posting behavior. Then, the authors explored the characteristics of textual content in mobile reviews compared to reviews written via traditional devices.

Findings

The authors' finding shows that the use of mobile devices negatively influences text-posting behavior. Compared to traditional devices, consumers are less likely to post texts in their reviews with mobile devices. Although consumers decide to post text comments in consumers' reviews, the quality of textual content is relatively low – short in length, with limited analytical thinking and less authenticity.

Originality/value

To the best of the authors' knowledge, no study has attempted to explore text generation in review-posting behaviors in the context of mobile channels. Also, the authors' findings show the negative effects of using mobile channels on the value of generated information, which is counterintuitive to previous research.
The impact of executive isolation of CEO on CXOs attrition: a case study of a not-for-profit organization
Authors: Kappal Rishi , Mishra Dharmesh K.
Published: July 2022

Purpose

This paper aims to explore the interlinkage and association of executive isolation at the workplace faced by Chief Executive Officer (CEO) of a not-for-profit organizations (NPOs) and its impact on the attrition at the C-Suite Professionals (CXO), Direct reports of CEO levels.

Design/methodology/approach

Executive isolation at top management with reference to the CEO level has emerged as a major challenge that is faced by NPOs with the effect being multiplied by the pandemic and remote working. This paper intends to examine the relevance of the impact of executive isolation experienced by top management leading to increase in the attrition at the CXO levels in NPOs due to their increasing dissatisfaction. To make a thorough study, a detailed literature review has been done followed by qualitative research methods of individual interviews, group interviews and surveys to ascertain the implications of CXO-level executive isolation on the CXOs attrition in NPOs.

Findings

The executive isolation experienced by CEOs makes them develop certain preconceived set of beliefs. By being isolated from the direct report CXOs and action on the ground and working from a remote location, they tend to inculcate their own decisions into the direct reports, thereby depriving them of authority and autonomy. This starts leading to the high level of CXO attrition.

Research limitations/implications

This paper has tried to study the linkage of the executive isolation at top management with the levels of CXO dissatisfaction leading to attrition at NPOs. This topic appears to be much-needed to be understood, especially when the new normal of work is being redefined.

Practical implications

The paper enumerates that the NPOs can attempt to deal with the challenges of engaging CXOs through virtual working; however, the mindfulness can be impacted by the experiences of executive isolation at management levels. This, in turn, can lead to lower morale, compromised performance resulting in CXO-level dissatisfaction and attritions.

Originality/value

With the limited awareness about executive isolation and its multiplier effect due to the pandemic, NPOs, like other enterprises, had to resort to virtual working. However, executive isolation at management levels apparently leads to reduction in the CXO-level engagement with the teams under them and with the CEO to which they report. This aspect can lead to the NPOs not being able to achieve their impact objectives during the outward turbulence and inward challenges of CXO-level attritions because of the CXO-level dissatisfaction.