bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered Functional Connectivity in Children with ADHD Revealed by Scalp EEG: An ERP Study
Authors: Chen Chunli , Yang Huan , Du Yasong , Zhai Guangzhi , Xiong Hesheng , Yao Dezhong , Xu Peng , Gong Jianhua , Yin Gang , Li Fali
Published: May 2021

Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental brain disorders in childhood. Despite extensive researches, the neurobiological mechanism underlying ADHD is still left unveiled. Since the deficit functions, such as attention, have been demonstrated in ADHD, in our present study, based on the oddball P3 task, the corresponding electroencephalogram (EEG) of both healthy controls (HCs) and ADHD children was first collected. And we then not only focused on the event-related potential (ERP) evoked during tasks but also investigated related brain networks. Although an insignificant difference in behavior was found between the HCs and ADHD children, significant electrophysiological differences were found in both ERPs and brain networks. In detail, the dysfunctional attention occurred during the early stage of the designed task; as compared to HCs, the reduced P2 and N2 amplitudes in ADHD children were found, and the atypical information interaction might further underpin such a deficit. On the one hand, when investigating the cortical activity, HCs recruited much stronger brain activity mainly in the temporal and frontal regions, compared to ADHD children; on the other hand, the brain network showed atypical enhanced long-range connectivity between the frontal and occipital lobes but attenuated connectivity among frontal, parietal, and temporal lobes in ADHD children. We hope that the findings in this study may be instructive for the understanding of cognitive processing in children with ADHD.
The Effects of Intensive Blood Pressure Control on Cardiovascular Outcomes Based on 10-Year ASCVD Risk Score: An Analysis of a Clinical Trial
Authors: Alborzi Alireza , Attar Armin , Sayadi Mehrab , Nouri Fatemeh
Published: May 2021

There is still controversy about whether clinicians should include cardiovascular disease (CVD) risk stratification into the consideration for treatment of hypertension. This was a post hoc analysis of the Systolic Blood Pressure Intervention Trial (SPRINT). A total of 9361 nondiabetic patients without a history of stroke were randomly assigned to the intensive-treatment group (with an SBP target of <120 mm Hg) and the standard-treatment group (with an SBP target of <140 mm Hg). The patients were categorized into four groups based on the Atherosclerotic Cardiovascular Disease (ASCVD) risk score. The groups contained participants with ASCVD < 7.5%, 7.5% ≤ ASCVD <10%, 10% ≤ ASCVD < 15%, and ASCVD ≥ 15%. The incidence of the primary outcome, secondary outcome, and serious adverse events was compared between the two groups. The primary outcome was a composite of nonfatal myocardial infarction (MI), acute coronary syndrome (ACS) not resulting in MI, stroke, acute decompensated heart failure (HF), or death from cardiovascular causes. The secondary outcomes consisted of the individual components of the primary outcome and all-cause death. Intensive blood pressure (BP) control significantly reduced the incidence of primary outcome event in patients with 10% ≤ ASCVD < 15% (hazard ratio (HR) 0.593; 95% confidence interval (CI) 0.361–0.975;

P

 = 0.039) and ASCVD ≥ 15% (HR 0.778; CI 0.644–0.940;

P

 = 0.009). Intensive BP control was also beneficial for the primary prevention of cardiovascular events in patients with an ASCVD risk of 7.5–10% (HR 0.187; 95% CI 0.040–0.862;

P

 = 0.032). However, intensive treatment was associated with higher incidence of hypotension and acute renal failure in participants with ASCVD ≥ 15%. In patients without diabetes mellitus and prior stroke who had a 10-year risk of cardiovascular events above 10% based on the ASCVD risk score, intensive BP control played an important role in the reduction of major cardiovascular events. Additionally, intensive treatment would be beneficial for primary prevention in patients with ASCVD ≥ 7.5% without previous history of any cardiovascular disorders. Trial registration: ClinicalTrials.gov number; the trial is registered with NCT01206062.
Selective Requirement of MYB for Oncogenic Hyperactivation of a Translocated Enhancer in Leukemia
Authors: Smeenk Leonie , Ottema Sophie , Mulet-Lazaro Roger , Ebert Anja , Havermans Marije , Varea Andrea Arricibita , Fellner Michaela , Pastoors Dorien , van Herk Stanley , Erpelinck-Verschueren Claudia , Grob Tim , Hoogenboezem Remco M. , Kavelaars François G. , Matson Daniel R. , Bresnick Emery H. , Bindels Eric M. , Kentsis Alex , Zuber Johannes , Delwel Ruud
Published: May 2021

In acute myeloid leukemia (AML) with inv(3)(q21;q26) or t(3;3)(q21;q26), a translocated GATA2 enhancer drives oncogenic expression of EVI1. We generated an EVI1-GFP AML model and applied an unbiased CRISPR/Cas9 enhancer scan to uncover sequence motifs essential for EVI1 transcription. Using this approach, we pinpointed a single regulatory element in the translocated GATA2 enhancer that is critically required for aberrant EVI1 expression. This element contained a DNA-binding motif for the transcription factor MYB, which specifically occupied this site at the translocated allele and was dispensable for GATA2 expression. MYB knockout as well as peptidomimetic blockade of CBP/p300-dependent MYB functions resulted in downregulation of EVI1 but not of GATA2. Targeting MYB or mutating its DNA-binding motif within the GATA2 enhancer resulted in myeloid differentiation and cell death, suggesting that interference with MYB-driven EVI1 transcription provides a potential entry point for therapy of inv(3)/t(3;3) AMLs.

Significance:

We show a novel paradigm in which chromosomal aberrations reveal critical regulatory elements that are nonfunctional at their endogenous locus. This knowledge provides a rationale to develop new compounds to selectively interfere with oncogenic enhancer activity.

This article is highlighted in the In This Issue feature, p. 2659
Birthweight, Childhood Body Mass Index, Height and Growth, and Risk of Polycystic Ovary Syndrome
Authors: Aarestrup Julie , Pedersen Dorthe C. , Thomas Peter E. , Glintborg Dorte , Holm Jens-Christian , Bjerregaard Lise G. , Baker Jennifer L.
Published: May 2021

Introduction: Adult obesity is linked with polycystic ovary syndrome (PCOS), but the importance of body size at ages before PCOS is diagnosed is unknown. Objective: To investigate associations between a woman’s own birthweight, childhood body mass index (BMI), height and growth patterns in relation to her risk of PCOS. Methods: We included 65,665 girls from the Copenhagen School Health Records Register, born in the period 1960–1996, with information on birthweight and measured weight and height at the ages of 7–13 years. Overweight was defined using International Obesity Task Force (IOTF) criteria. From the Danish National Patient Register, 606 women aged 15–50 years were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox regression analysis. Results: Birthweight was not associated with PCOS. At the age of 7–13 years, girls with overweight had a higher risk of developing PCOS than girls without overweight; HR 2.83 (95% CI 2.34–3.42) at age 7 years and 2.99 (95% CI 2.38–3.76) at age 13 years. Furthermore, girls with overweight at both 7 and 13 years had a higher risk of developing PCOS than girls without overweight or overweight at only one age. Height was positively associated with PCOS risk at all ages. Girls who were persistently tall or changed from tall to average height had a higher risk of developing PCOS than girls with average height growth. Conclusion: Overweight and tall stature in childhood are positively associated with PCOS risk, but birthweight is not.
Association of Cognitive Function Screening Results with Adherence and Performance in a Pedometer-Based Intervention
Authors: Sheshadri Anoop , Kittiskulnam Piyawan , Delgado Cynthia , Sudore Rebecca L. , Lai Jennifer C. , Johansen Kirsten L.
Published: May 2021

Introduction: A randomized, controlled trial of a pedometer-based walking intervention with weekly activity goals led to increased walking among dialysis patients. We examined whether impairment per cognitive function screening is associated with adherence and performance in the intervention. Methods: Thirty dialysis patients were randomly assigned to a 3-month pedometer-based intervention with weekly goals. Participants were administered the Telephone Interview of Cognitive Status (TICS), a test of global mental status. We examined the association of levels of impairment on the TICS (≥33: unimpaired, 26–32: ambiguous impairment, 21–25: mild cognitive impairment [MCI]) with adherence, achieving weekly goals, and increasing steps, physical performance (Short Physical Performance Battery, SPPB), and self-reported physical function (PF) through multivariable linear mixed-model and logistic regression analyses adjusted for age, sex, BMI, dialysis modality, baseline steps, baseline SPPB, and stroke status. Results: One-third of participants were unimpaired, and 13% had MCI. Participants with worse results on cognitive function screening missed more calls and completed fewer weekly goals than participants with better results. During the intervention, a worse result on cognitive function screening was associated with smaller increases in steps compared to those without impairment: (ambiguous: −620 [95% CI −174, −1,415], MCI: −1,653 [95% CI −120, −3,187]); less improvement in SPPB (ambiguous: −0.22 points [95% CI −0.08, −0.44], MCI: −0.45 [95% CI −0.13, −0.77]); and less improvement in PF (ambiguous: −4.0 points [95% CI −12.2, 4.1], MCI: −14.0 [95% CI −24.9, −3.1]). During the postintervention period, a worse result on cognitive function screening was associated with smaller increases in SPPB (ambiguous: −0.54 [95% CI −1.27, 0.19], MCI: −0.97 [95% CI −0.37, −1.58]) and PF (ambiguous: −3.3 [95% CI −6.5, −0.04], MCI: −10.5 [95% CI −18.7, −2.3]). Discussion/Conclusion: Participants with worse results on cognitive function screening had worse adherence and derived less benefit from this pedometer-based intervention. Future exercise interventions should be developed incorporating methods to address cognitive impairment, for example, by including caregivers when planning such interventions.
Two new species of Amphinemura (Plecoptera: Nemouridae) from Taiwan Province on the southeast coast of China
Authors: ZHAO MENG-YUAN , DU YU-ZHOU
Published: May 2021

Two new species of Amphinemura were described and illustrated from Taiwan Province of China: Amphinemura reni Du & Zhao, sp. nov. and Amphinemura triquetra Zhao & Du, sp. nov. The morphological characteristics of the new species were compared to related taxa. Additionally, a key to the adult males of Amphinemura known from Taiwan Province of China was given in this paper.
Targeting Matrix Metalloproteinases: A Potential Strategy for Improving Cell Transplantation for Nervous System Repair
Authors: Tseng Yu-Ting , Chen Mo , John James St , Ekberg Jenny
Published: May 2021

Cell transplantation shows promise for repair of the injured nervous system, including spinal cord injury (SCI) and peripheral nerve injury (PNI). There are, however, still problems hampering these therapies moving from bench to bedside, and the methods need optimization. Three-dimensional (3D) cell culture systems are suggested to improve outcomes, bridging the gap between the in vitro and in vivo environments. In such constructs, cells are allowed to interact with each other and with the extracellular matrix (ECM) in 3D as they do in vivo. Transplanting cells in 3D constructs, rather than in suspension, is thought to promote cell survival and maintain important cellular behaviors. One such critical behavior is cell migration into and within the injury site. Understanding and controlling the migratory capability of 3D-cultured cells is therefore pivotal for developing better transplantation techniques. ECM remodelling can influence numerous cellular functions, including cell migration and matrix metalloproteinases (MMPs) are important enzymes for ECM modulation. Here, we discuss the idea of modulating MMPs to control cell migration in 3D culture systems, which can improve the therapeutic potential of cells transplanted in 3D.
Stability study of concentrate-solvent mixture & infusion solutions of Jevtana® cabazitaxel for extended multi-dosing
Authors: Hedvig Arnamo A , Huitema Alwin D.R , Beijnen Jos H , Nuijen Bastiaan
Published: May 2021

Aim/Background

In this study, the prolonged physical and chemical stability of the anticancer agent cabazitaxel, commercially available as Jevtana®, was examined. Both concentrate-solvent mixture and infusion solution were examined with the aim to extend the use of multidose left-over cabazitaxel and infusion solutions and with that reduce financial and environmental waste.

Methods

A validated stability-indicating high-pressure liquid chromatography (HPLC) method with ultraviolet (UV) and photodiode array (PDA) detection was used to examine the purity and any degradation of cabazitaxel. The concentrate-solvent mixture and infusion solution samples that were tested had been stored out of the range of the criteria stated in the summary of product characteristics (SmPC). The concentrate-solvent mixtures were stored at 3–5°C, 18–21°C, and 40 °C, whereas the infusion solution was stored at 3–5°C. All samples were tested at t = 0, t = 1 week and t = 2 weeks.

Results

All samples showed that purity and concentration had remained within the criteria of <5% as stated in the European Pharmacopoeia. However, the concentrate-solvent mixtures stored at 18-21°C and 40 °C showed a degradation product forming in all the samples lowering the purity of the samples from 100% to 99.91% and 98.20% respectively, whereas all samples stored at 3–5°C remained at 100%.

Conclusion

Concentrate-solvent mixture and infusion solution of cabazitaxel, Jevtana®, can be used up to 2 weeks after preparation if stored at 3–5°C and prepared under aseptic conditions.
A case report of individualized ventilation in a COVID-19 patient – new possibilities and caveats to consider with flow-controlled ventilation
Authors: Spraider Patrick , Putzer Gabriel , Breitkopf Robert , Abram Julia , Mathis Simon , Glodny Bernhard , Martini Judith
Published: May 2021

Background

Flow-controlled ventilation (FCV) is a novel ventilation method increasingly being used clinically, particularly during the current COVID-19 pandemic. However, the continuous flow pattern in FCV during inspiration and expiration has a significant impact on respiratory parameters and ventilatory settings compared to conventional ventilation modes. In addition, the constant flow combined with direct intratracheal pressure measurement allows determination of dynamic compliance and ventilation settings can be adjusted accordingly, reflecting a personalized ventilation approach.

Case presentation

A 50-year old women with confirmed SARS-CoV-2 infection suffering from acute respiratory distress syndrome (ARDS) was admitted to a tertiary medical center. Initial ventilation occurred with best standard of care pressure-controlled ventilation (PCV) and was then switched to FCV, by adopting PCV ventilator settings. This led to an increase in oxygenation by 30 %. Subsequently, to reduce invasiveness of mechanical ventilation, FCV was individualized by dynamic compliance guided adjustment of both, positive end-expiratory pressure and peak pressure; this intervention reduced driving pressure from 18 to 12 cm H2O. However, after several hours, compliance further deteriorated which resulted in a tidal volume of only 4.7 ml/kg.

Conclusions

An individualized FCV approach increased oxygenation parameters in a patient suffering from severe COVID-19 related ARDS. Direct intratracheal pressure measurements allow for determination of dynamic compliance and thus optimization of ventilator settings, thereby reducing applied and dissipated energy. However, although desirable, this personalized ventilation strategy may reach its limits when lung function is so severely impaired that patient’s oxygenation has to be ensured at the expense of lung protective ventilation concepts.
Genome-wide analysis of DNA methylation and risk of cardiovascular disease in a Chinese population
Authors: Gao Yan , Pang Huifang , Chen Bowang , Wu ChaoQun , Wang Yanping , Hou Libo , Wang Siming , Sun Dianjianyi , Zheng Xin
Published: May 2021

Background

Systemic studies of association of genome-wide DNA methylated sites with cardiovascular disease (CVD) in prospective cohorts are lacking. Our aim was to identify DNA methylation sites associated with the risk of CVD and further investigate their potential predictive value in CVD development for high-risk subjects.

Methods

We performed an epigenome-wide association study (EWAS) to identify CpGs related to CVD development in a Chinese population.We adopted a nested case–control design based on data from China PEACE Million Persons Project. A total of 83 cases who developed CVD events during follow-up and 83 controls who were matched with cases by age, sex, BMI, ethnicity, medications treatment and behavior risk factors were included in the discovery stage. Genome-wide DNA methylation from whole blood was detected using Infinium Human Methylation EPIC Beadchip (850 K). For significant CpGs [FDR(false discovery rate) < 0.005], we further validated in an independent cohort including 38 cases and 38 controls.

Results

In discovery set, we identified 8 significant CpGs (FDR < 0.005) associated with the risk of CVD after adjustment for cell components, demographic and cardiac risk factors and the first 5 principal components. Two of these identified CpGs (cg06901278 and cg09306458 in UACA) were replicated in another independent set (p < 0.05). Enrichment analysis in 787 individual genes from 1036 CpGs in discovery set revealed a significant enrichment for anatomical structure homeostasis as well as regulation of vesicle-mediated transport. Receiver operating characteristic (ROC) analysis showed that the model combined 8 CVD-related CpGs with baseline characteristics showed much better predictive effect for CVD occurrence compared with the model with baseline characteristics only [AUC (area under the curve) = 0.967, 95% CI (0.942 − 0.991); AUC = 0.621, 95% CI (0.536 − 0.706); p = 9.716E-15].

Conclusions

Our study identified the novel CpGs associated with CVD development and revealed their additional predictive power in the risk of CVD for high-risk subjects.
Distinguishing between household headship with and without power and its association with subjective well-being among older adults: an analytical cross-sectional study in India
Authors: Srivastava Shobhit , Singh S. K. , Kumar Manish , Muhammad T.
Published: May 2021

Background

The status of household headship accorded to the older members of the family is often symbolic and seldom vested with some control over resources. The increased dependency and diminished ability to contribute to household economy are major factors that lead to a decline in the respect accorded to older people and their status in the family. The present study aimed to understand the distinction between the functional and nominal household headship status of older adults based on their decision-making power and examine how it is associated with their subjective well-being.

Method

The present research used data from the 'Building a Knowledge Base on Population Aging in India' (BKPAI) which is nationally representative. The survey was conducted in 2011, across seven states of India. Descriptive statistics along with percentage distribution were calculated for subjective well-being over explanatory variables. For finding the association between subjective well-being over explanatory variables, binary logistic regression model was used.

Results

The mean age of the study population was 68 years [CI: 67.8–68.2]. About 5 % of older adults had nominal while 95% had functional headship status. The prevalence of low subjective well-being (LSWB) was significantly higher among older adults with nominal headship status (58%) than functional headship status (23%). After controlling for several other variables, older adults with nominal headship status were 59% significantly more likely to have low subjective well-being than individuals with functional headship status (OR = 1.59; 95% CI: 1.10, 2.31). Further, older adults with psychological distress, chronic morbidity, poor self-reported health, no community involvement and no one to trust on were at higher risk of LSWB than their counterparts.

Conclusions

Findings suggest that older adults who do not have a household headship with power with active participation in household decision-making as well as those who have no involvement in social activities or have poor health conditions need to be given more attention. Thus, to keep a large proportion of older population gainfully engaged, their care and support should be ensured via providing appropriate services that would enhance their roles and responsibilities and overall wellbeing.
Clinical efficacy of scaling and root planing with and without metronidazole on glycemic control: three-arm randomized controlled trial
Authors: Qureshi Ambrina , Bokhari Syed Akhtar Hussain , Haque Zeba , Baloch Akhtar Ali , Zaheer Sidra
Published: May 2021

Background

Treating periodontitis through non-surgical periodontal therapy (NSPT) may improve glycemic control in type-2 Diabetes Mellitus (T2DM) patients. However, the evidence to maintain this improvement beyond four months is insufficient. Hence, this trial was conducted to assess clinical efficacy of NSPT on glycemic control in T2DM patients.

Methods

This three-arm randomized controlled trial recruited 150 known T2DM participants (35–65 years), suffering from moderate to severe periodontitis, having HbA1c level ≥ 6.5% at baseline. Participants were followed up at 3 and 6 months. Intervention for test group-1 included scaling and root planing (SRP) with metronidazole (MET) and oral hygiene instructions (OHI). Test group-2 was intervened with SRP + OHI and control group with OHI only. Stata v. 14 was used to observe inter and intragroup mean changes in glycemic [glycated hemoglobin (HbA1c), fasting blood glucose (FBG)] and periodontal variables [bleeding on probing (BOP), periodontal pocket depth (PPD), clinical attachment loss (CAL)] using ANOVA and RMANOVA. Proportion of change in outcome variable (HbA1c) was assessed between treatment groups using chi-square test. Change was considered significant at p-value ≤ 0.05.

Results

A significant reduction was observed in BOP, PPD, CAL, HbA1c and FBG over time [p < 0.05]. Significant reductions were observed in same variables in both test groups in comparison to control arm [p < 0.05]. No change between the two test groups was observed [p > 0.05].

Conclusion

Scaling and root planing improves glycemic control of T2DM patients independently of the use of MET. Therefore, SRP after every 6 months may be suggested and included as a part of overall diabetes management for patients suffering from T2DM.

Clinical trial registration NCT 03,343,366 [Date of Registration: 17/11/2017]
Giant intracardiac thrombosis in an infant with leukaemia and prolonged COVID-19 viral RNA shedding: a case report
Authors: Aghaei Moghadam Ehsan , Mahmoudi Shima , Safari Sharari Alieh , Afsharipour Mehrnoush , Gorji Mojtaba , Navaeian Amene , Ghamari Azin , Mamishi Setareh
Published: May 2021

Background

COVID-19 can induce thrombotic disease both in the venous and arterial circulations, as a result of inflammation, platelet activation, endothelial dysfunction, and stasis. Although several studies have described the coagulation abnormalities and thrombosis in adult patients with COVID-19, there is limited data in children. Here, we present an 18-month-old boy with a prolonged SARS-CoV‐2 RNA shedding and chronic right atrial and superior vena cava (SVC) thrombosis.

Case presentation

An 18-month-old boy with acute lymphoblastic leukemia (ALL) (pre-B cell ALL) and a history of chemotherapy was referred to our center due to intermittent fever with unknown origin. a positive nasopharyngeal PCR for COVID-19 was reported and stayed positive for eight consecutive weeks The high-resolution computed tomography (HRCT) showed no sign of pulmonary embolism. Initial echocardiography indicated a semilunar thrombotic mass extending from right SVC into the right atrium without coronary or myocardial involvement. Enoxaparin was administered with continuous monitoring of the level of anti-Xa activity. The serial echocardiographic studies found a slow but continuous reduction in the mass size.

Conclusions

Our case shows that, as already described in adult patients, clinically relevant thrombosis can complicate the course of pediatric patients as well. In view of the specific and milder manifestations of COVID-19 in children, these complications may pose considerable diagnostic and therapeutic challenges.
Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets
Authors: Kim Sung-Hyun , Lim Key-Hwan , Yang Sumin , Joo Jae-Yeol
Published: May 2021

Brain tumors are associated with adverse outcomes despite improvements in radiation therapy, chemotherapy, and photodynamic therapy. However, treatment approaches are evolving, and new biological phenomena are being explored to identify the appropriate treatment of brain tumors. Long non-coding RNAs (lncRNAs), a type of non-coding RNA longer than 200 nucleotides, regulate gene expression at the transcriptional, post-transcriptional, and epigenetic levels and are involved in a variety of biological functions. Recent studies on lncRNAs have revealed their aberrant expression in various cancers, with distinct expression patterns associated with their instrumental roles in cancer. Abnormal expression of lncRNAs has also been identified in brain tumors. Here, we review the potential roles of lncRNAs and their biological functions in the context of brain tumors. We also summarize the current understanding of the molecular mechanisms and signaling pathways related to lncRNAs that may guide clinical trials for brain tumor therapy.
Stem cell therapies and benefaction of somatic cell nuclear transfer cloning in COVID-19 era
Authors: Singh Birbal , Mal Gorakh , Verma Vinod , Tiwari Ruchi , Khan Muhammad Imran , Mohapatra Ranjan K. , Mitra Saikat , Alyami Salem A. , Emran Talha Bin , Dhama Kuldeep , Moni Mohammad Ali
Published: May 2021

Background

The global health emergency of COVID-19 has necessitated the development of multiple therapeutic modalities including vaccinations, antivirals, anti-inflammatory, and cytoimmunotherapies, etc. COVID-19 patients suffer from damage to various organs and vascular structures, so they present multiple health crises. Mesenchymal stem cells (MSCs) are of interest to treat acute respiratory distress syndrome (ARDS) caused by SARS-CoV-2 infection.

Main body

Stem cell-based therapies have been verified for prospective benefits in copious preclinical and clinical studies. MSCs confer potential benefits to develop various cell types and organoids for studying virus-human interaction, drug testing, regenerative medicine, and immunomodulatory effects in COVID-19 patients. Apart from paving the ways to augment stem cell research and therapies, somatic cell nuclear transfer (SCNT) holds unique ability for a wide range of health applications such as patient-specific or isogenic cells for regenerative medicine and breeding transgenic animals for biomedical applications. Being a potent cell genome-reprogramming tool, the SCNT has increased prominence of recombinant therapeutics and cellular medicine in the current era of COVID-19. As SCNT is used to generate patient-specific stem cells, it avoids dependence on embryos to obtain stem cells.

Conclusions

The nuclear transfer cloning, being an ideal tool to generate cloned embryos, and the embryonic stem cells will boost drug testing and cellular medicine in COVID-19.
The effects of ENSO, climate change and human activities on the water level of Lake Toba, Indonesia: a critical literature review
Authors: Irwandi Hendri , Rosid Mohammad Syamsu , Mart Terry
Published: May 2021

This research quantitatively and qualitatively analyzes the factors responsible for the water level variations in Lake Toba, North Sumatra Province, Indonesia. According to several studies carried out from 1993 to 2020, changes in the water level were associated with climate variability, climate change, and human activities. Furthermore, these studies stated that reduced rainfall during the rainy season due to the El Niño Southern Oscillation (ENSO) and the continuous increase in the maximum and average temperatures were some of the effects of climate change in the Lake Toba catchment area. Additionally, human interventions such as industrial activities, population growth, and damage to the surrounding environment of the Lake Toba watershed had significant impacts in terms of decreasing the water level. However, these studies were unable to determine the factor that had the most significant effect, although studies on other lakes worldwide have shown these factors are the main causes of fluctuations or decreases in water levels. A simulation study of Lake Toba's water balance showed the possibility of having a water surplus until the mid-twenty-first century. The input discharge was predicted to be greater than the output; therefore, Lake Toba could be optimized without affecting the future water level. However, the climate projections depicted a different situation, with scenarios predicting the possibility of extreme climate anomalies, demonstrating drier climatic conditions in the future. This review concludes that it is necessary to conduct an in-depth, comprehensive, and systematic study to identify the most dominant factor among the three that is causing the decrease in the Lake Toba water level and to describe the future projected water level.
Non-functioning oxyphilic parathyroid carcinoma: a case report
Authors: Sen Masaomi , Nagaoka Ryuta , Kazusaka Hiroko , Matsui Mami , Saitou Marie , Sugitani Iwao , Sakatani Takashi , Kameyama Kaori
Published: May 2021

Background

Non-functioning parathyroid carcinoma is an extremely rare malignancy among endocrine tumors. We report a case in which non-functional oxyphilic parathyroid carcinoma was diagnosed from clinical symptoms and pathological diagnosis.

Case presentation

The patient was a 42-year-old man with no medical or family history of note. He had presented to a local hospital with a neck mass 2 months earlier. Medullary thyroid carcinoma was diagnosed and he was referred to our department. A 3.5-cm mass was observed in the left thyroid lobe. Laboratory data for thyroid functions, thyroglobulin, anti-thyroglobulin antibodies, anti-thyroid peroxidase antibodies, serum calcium, and parathyroid hormone (PTH) were all within normal ranges. Ultrasonography revealed a 40-mm irregular, hypoechoic mass throughout the left thyroid lobe. Follicular thyroid tumor was suspected from fine-needle aspiration cytology. Left lobectomy was performed. Pathological features revealed a thick fibrous capsule around the tumor, and a thick fibrous band was observed inside the tumor. Both capsular invasions and vascular invasions were observed. Tumor cells were eosinophilic and displayed solid growth. Immunohistochemically, tumor cells were negative for thyroid transcription factor-1, negative for thyroglobulin, negative for chromogranin A (positive for normal parathyroid tissue within the nodule), positive for PTH, and positive for parafibromin. Ki-67 labeling index was 10%. Based on these findings, non-functional oxyphilic parathyroid carcinoma was diagnosed. One and a half years postoperatively, calcium and PTH were within normal ranges, and he has shown no evidence of recurrence or metastasis.

Conclusions

Non-functioning oxyphilic parathyroid carcinoma is an extremely rare malignancy, and definitive diagnosis is difficult to obtain preoperatively. Few reports have been made worldwide, and information on the long-term prognosis is scarce. Long-term surveillance by imaging is mandatory, since no indices that can be used as a marker for postoperative recurrence and metastasis have been identified.
Managing restricted patients in acute, non-secure in-patient services: clinical, ethical and resource implications of long waits for a response from the Ministry of Justice
Authors: Sharma Gunjan , Brown Penelope , Rehman Ijaz Ur , Chesney Edward
Published: May 2021

Aims and method

In-patients subject to Section 37/41 of the Mental Health Act 1983 (MHA) require permission from the Ministry of Justice (MoJ) for leave, transfer and discharge. This study aimed to quantify the time spent waiting for the MoJ to respond to requests, using data on restricted patients recalled to a non-forensic unit over 8 years.

Results

Eleven admissions were identified. The mean total time waiting for response was 95 days per admission, with an estimated cost of £40 922 per admission.

Clinical implications

Current procedures may contribute to considerable increases in length of stay. This goes against the principles of the MHA, as non-secure services rarely provide the range of interventions which justify prolonged admission. We suggest several ways to resolve this issue, including broadening the guidance for the use of voluntary admissions and civil sections, and allowing clinicians to make decisions on leave and transfer where there is little risk.
Characterize, Optimize, and Harmonize: Caring for Older Adults With Hematologic Malignancies
Authors: Wildes Tanya M. , Artz Andrew S.
Published: May 2021

With the aging of the population, the number of older adults with hematologic malignancies is growing, and treatment paradigms for these patients are rapidly evolving. Use of allogeneic stem cell transplant has been expanding to include septuagenarians but remains a potentially morbid procedure, creating an opportunity for a geriatric-focused evaluation to improve assessment of the individual’s risk in undergoing the procedure. Although age alone should not be the sole determinant for transplant eligibility, geriatric assessment often identifies vulnerabilities that are not captured in assessing performance status and comorbidities alone. Those vulnerabilities may be optimized in an approach employing three sequential steps: characterize resiliency, bolster resilience, and harmonize with patient goals. Data are emerging that show that this approach is associated with lower nonrelapse mortality, shorter length of stay, and better survival after transplant. In older adults with myeloma, treatment recommendations also aim to balance the expected efficacy and toxicity profile and incorporate the patient’s goals and preferences. Assessment of frailty allows for more personalized estimates of risk of toxicity. Currently, the European Myeloma Network currently recommends using the International Myeloma Working Group frailty scale as a standard approach to defining frail or at-risk populations with myeloma. In addition to treatment selection, the care of older adults with myeloma must include consideration of other issues, including reducing early mortality with antibiotic prophylaxis, polypharmacy, depression, cognition, and falls. Overall, appreciation of the aging-associated vulnerabilities will allow for the ultimate personalized care and treatment of older adults with hematologic malignancies.
Genetic Analysis of Pediatric Primary Adrenal Insufficiency of Unknown Etiology: 25 Years’ Experience in the UK
Authors: Buonocore Federica , Maharaj Avinaash , Qamar Younus , Koehler Katrin , Suntharalingham Jenifer P , Chan Li F , Ferraz-de-Souza Bruno , Hughes Claire R , Lin Lin , Prasad Rathi , Allgrove Jeremy , Andrews Edward T , Buchanan Charles R , Cheetham Tim D , Crowne Elizabeth C , Davies Justin H , Gregory John W , Hindmarsh Peter C , Hulse Tony , Krone Nils P , Shah Pratik , Shaikh M Guftar , Roberts Catherine , Clayton Peter E , Dattani Mehul T , Thomas N Simon , Huebner Angela , Clark Adrian J , Metherell Louise A , Achermann John C
Published: May 2021

Context

Although primary adrenal insufficiency (PAI) in children and young people is often due to congenital adrenal hyperplasia (CAH) or autoimmunity, other genetic causes occur. The relative prevalence of these conditions is poorly understood.

Objective

We investigated genetic causes of PAI in children and young people over a 25 year period.

Design, Setting and Participants

Unpublished and published data were reviewed for 155 young people in the United Kingdom who underwent genetic analysis for PAI of unknown etiology in three major research centers between 1993 and 2018. We pre-excluded those with CAH, autoimmune, or metabolic causes. We obtained additional data from NR0B1 (DAX-1) clinical testing centers.

Intervention and Outcome Measurements

Genetic analysis involved a candidate gene approach (1993 onward) or next generation sequencing (NGS; targeted panels, exomes) (2013-2018).

Results

A genetic diagnosis was reached in 103/155 (66.5%) individuals. In 5 children the adrenal insufficiency resolved and no genetic cause was found. Pathogenic variants occurred in 11 genes: MC2R (adrenocorticotropin receptor; 30/155, 19.4%), NR0B1 (DAX-1; 7.7%), CYP11A1 (7.7%), AAAS (7.1%), NNT (6.5%), MRAP (4.5%), TXNRD2 (4.5%), STAR (3.9%), SAMD9 (3.2%), CDKN1C (1.3%), and NR5A1/steroidogenic factor-1 (SF-1; 0.6%). Additionally, 51 boys had NR0B1 variants identified through clinical testing. Although age at presentation, treatment, ancestral background, and birthweight can provide diagnostic clues, genetic testing was often needed to define the cause.

Conclusions

PAI in children and young people often has a genetic basis. Establishing the specific etiology can influence management of this lifelong condition. NGS approaches improve the diagnostic yield when many potential candidate genes are involved.
Women in Academic Economics: Have We Made Progress?
Authors: Ginther Donna K. , Kahn Shulamit
Published: May 2021

This study uses data from Academic Analytics to examine gender differences in promotion to associate professor in economics. We found that women in economics were 15 percent less likely to be promoted to associate professor after controlling for cumulative publications, citations, grants, and grant dollars. In contrast, we found no significant gender differences in promotion in other fields including biomedical science, physical science, political science, mathematics and statistics, and engineering. We separated the sample by the research intensity of institutions and found suggestive evidence that these results were being driven by less research-intensive institutions.
“Placebo Tests” for the Impacts of Air Pollution on Health: The Challenge of Limited Health Care Infrastructure
Authors: Guidetti Bruna , Pereda Paula , Severnini Edson
Published: May 2021

"Placebo tests" are normally used to support evidence of pollution impacts on health outcomes. In this study, we argue that one should be cautious to proceed with falsification tests. We examine how a large metropolitan area in Brazil copes with increased health-care demand due to high air pollution under hospital capacity constraints. Using wind as an instrument, we find that the pollution exposure increases pediatric hospitalization for respiratory diseases while the number of planned procedures decreases in public hospitals. On average, for every four additional pollution-related admissions, one elective care procedure is displaced. Urgent procedures are not displaced.
Ambiguous Air Pollution Effects of China’s COVID-19 Lock-down
Authors: Almond Douglas , Du Xinming , Karplus Valerie J. , Zhang Shuang
Published: May 2021

Reductions in ambient pollution have been suggested as a "silver lining" to the COVID-19 pandemic. We analyze China's pollution monitor data and account for the large annual improvements in air quality following the Lunar New Year, which essentially coincided with lock-downs. With the exception of nitrogen dioxide, China's air quality improvements in 2020 are smaller than we should expect near the pandemic's epicenter, Hubei province. We see smaller improvements in sulfur dioxide than expected, while ozone concentrations roughly doubled in Hubei. Similar patterns are found for the six provinces neighboring Hubei. We conclude that COVID-19 had ambiguous impacts on China's air quality.
Nominal Wage Adjustments during the Pandemic Recession
Authors: Grigsby John , Hurst Erik , Yildirmaz Ahu , Zhestkova Yulia
Published: May 2021

In this paper, we show that the pandemic recession has led to frequent cuts in nominal wages. Within three months in 2020, as many wage cuts had occurred as occurred throughout the Great Recession. Unlike employment declines, wage cuts were concentrated at the top of the wage distribution. However, these cuts have been relatively short lived, particularly among high earners. Finally, wage cuts have been concentrated in firms that have seen large employment declines. Wage cuts appear not to be a substitute for cutting employment, at least when the shock to labor demand is this large.
COVID-19 and the Costs of Deadly Disasters
Authors: Ludvigson Sydney C. , Ma Sai , Ng Serena
Published: May 2021

Using monthly data on costly natural disasters affecting the United States over the last 40 years, we estimate 2 time series models and use them to generate predictions about the impact of COVID-19. We find that while our models yield reasonable estimates of the impact on industrial production and the number of scheduled flight departures, they underestimate the unprecedented changes in the labor market.
Border Carbon Adjustments When Carbon Intensity Varies across Producers: Evidence from California
Authors: Fowlie Meredith , Petersen Claire , Reguant Mar
Published: May 2021

Governments taxing carbon emissions within their jurisdiction can impose a commensurate tax on emissions embodied in imports in order to mitigate emissions leakage. California offers a rare opportunity to investigate how such a border carbon adjustment (BCA) is working in practice. Experience to date highlights important tensions between greenhouse gas accounting accuracy, market efficiency, and concerns about trade protectionism. We simulate electricity market outcomes under BCA designs that differ in terms of how the carbon intensity of imports is assessed. Simulations suggest significant potential for leakage via resource shuffling. Realized emissions outcomes indicate that this potential has not been fully realized.
Trends in US Spatial Inequality: Concentrating Affluence and a Democratization of Poverty
Authors: Gaubert Cecile , Kline Patrick , Vergara Damián , Yagan Danny
Published: May 2021

We use Bureau of Economic Analysis, census, and Current Population Survey data to study trends in income inequality across US states and counties from 1960-2019. Both states and counties have diverged in terms of per capita pretax incomes since the late1990s, with transfers serving to dampen this divergence. County incomes have been diverging since the late 1970s. These trends in mean income mask opposing patterns among top-and bottom-income quantiles. Top incomes have diverged markedly across states since the late 1970s. In contrast, bottom-income quantiles and poverty rates have converged across areas in recent decades.
Jackson, the Bank War, and the Legacy of the Second Bank of the United States
Authors: Rousseau Peter L.
Published: May 2021

President Jackson vetoed the bill to recharter the Second Bank of the United States on July 10, 1832. I describe events leading to the veto and through the bank's dissolution in 1836 using private correspondence and official government documents. These sources reveal a political process through which charges against the bank took hold, accomplices and backup plans were lined up, and the bank was ultimately destroyed with the assistance of chartered banks in New York City. Although the aggressive means by which the bank was dismantled led to a system-wide financial failure and recession in the short term, the long-run outcome was likely a wider diffusion of banking services and a more efficient allocation of capital. The Federal Reserve benefited from applying a more rigorous regulatory structure onto the grid that the populists, free bankers, and National Banking System established.
Preparing for a Pandemic: Accelerating Vaccine Availability
Authors: Ahuja Amrita , Athey Susan , Baker Arthur , Budish Eric , Castillo Juan Camilo , Glennerster Rachel , Kominers Scott Duke , Kremer Michael , Lee Jean , Prendergast Canice , Snyder Christopher M. , Tabarrok Alex , Tan Brandon Joel , Wie˛cek Witold
Published: May 2021

Vaccinating the world's population quickly in a pandemic has enormous health and economic benefits. We analyze the problem faced by governments in determining the scale and structure of procurement for vaccines. We analyze alternative approaches to procurement, arguing that buyers should directly fund manufacturing capacity and shoulder most of the risk of failure while maintaining some direct incentives for speed. We analyzed the optimal portfolio of vaccine investments for countries with different characteristics as well as the implications for international cooperation. Our analysis, considered in light of the experience of 2020, suggests lessons for future pandemics.
Private and Social Returns to R&D: Drug Development and Demographics
Authors: Benmelech Efraim , Eberly Janice , Papanikolaou Dimitris , Krieger Joshua
Published: May 2021

Investment in intangible capital such as R&D has increased dramatically since the 1990s. However, productivity growth remains sluggish in recent years. One potential reason is that a significant share of the increase in intangible investment is geared toward consumer products such as pharmaceutical drugs with limited spillovers to productivity. We document that a significant share of R&D spending in the United States is done by pharmaceutical firms and geared to developing drugs for older patients. Increased life expectancy and quality of life for the elderly increases welfare but may not be reflected in estimates of total factor productivity.
The Economics of Crisis Innovation Policy: A Historical Perspective
Authors: Gross Daniel P. , Sampat Bhaven N.
Published: May 2021

Since the beginning of the COVID-19 pandemic, policymakers, researchers, and journalists have made comparisons to World War II. In 1940, a group of top US science administrators organized a major coordinated research effort to support the Allied war effort, including significant investments in medical research that yielded innovations like mass-produced penicillin, antimalarials, and a flu vaccine. We draw on this episode to discuss the economics of crisis innovation. Since the objectives of crisis R&D are different than ordinary R&D, we argue that appropriate R&D policy in a crisis requires going beyond the standard Nelson-Arrow framework for research policy.
The Association between Wealth Inequality and Socioeconomic Outcomes
Authors: Ali Omer , Darity William A. , Janz Avra , Sánchez Marta
Published: May 2021

We investigate whether inequality in wealth distribution is broadly associated with adverse socioeconomic outcomes across countries. There are few studies that investigate these relationships, likely due to data limitations. On the other hand, a substantial body of work suggests that income inequality correlates with undesirable outcomes. This paper evaluates the relationship between measures of wealth inequality and a number of outcomes across countries in a unified estimation framework that circumvents publication bias. While we fail to find support for a broad negative association, we do find a negative correlation between wealth inequality and institutional quality.