bluuebunny/crossref_metadata_2025 huggingface dataset:
Prolonged Honeymoon Period in a Thai Patient With Adult-Onset Type 1 Diabetes Mellitus - Metabolic Flexibility in Autoimmune Diabetes?
Authors: Thewjitcharoen Yotsapon , Wanothayaroj Ekgaluck , Chatchomchuan Waralee , Jaita Haruethai , Nakasatien Soontaree , Butadej Siriwan , Krittiyawong Sirinate , Himathongkam Thep
Published: May 2021

Background: ‘Honeymoon’ period among people with type 1 diabetes mellitus (T1DM) refers to the period of time (mostly less than 1 year) which beta-cell is still able to produce insulin to maintain good glycemic control shortly following the development of diabetes. This phenomenon remained incompletely understood but previous studies showed that absence of diabetic ketoacidosis (DKA) at initial presentation, short duration of symptoms, older age at presentation, and strenuous exercise could be potential factors. Herein, we report a 24-year old Thai patient with T1DM who has been in sustained complete remission for more than 5 years while he is maintaining low carbohydrate intake and regular exercise.

Clinical Case: A 24-year-old male presented with a 6-month history of polyuria, polydipsia and weight loss of 15 kilograms (baseline BMI at 27.8 kg/m2). His initial laboratory data showed plasma glucose 398 mg/dL and A1C 9.3%. No ketonemia was found. He was diagnosed with stage 3 of Type 1 DM based on clinical presentation and positive pancreatic auto-antibodies (anti-GAD and anti-IA2). Euthyroid Hashimoto’s thyroiditis was also diagnosed based on his enlarged thyroid gland and positive thyroid auto-antibodies. He was started on basal-bolus insulin regimen for only 2 month and then A1C reversed to 5.9% within 2 months. Insulin was gradually withdrawn and completely stopped. Mixed meal stimulation test (MMST) was firstly evaluated at the second year of his diagnosis. The result revealed stimulated C-peptide at 5.5 ng/dL. Next-generation sequencing panel for monogenic diabetes revealed negative results. The patient maintains healthy lifestyle habit with low carbohydrate intake and regular exercise 5–6 times per week. His body weight was maintained at 60–63 kilograms during the past 4 years. His A1C was maintained between 5.0 to 6.0% without any anti-diabetic medication for more than 5 years. Repeated MMST in every 6–12 months still revealed preserved beta-cell functions and normal stimulated plasma glucose. Interestingly, repeated pancreatic auto-antibodies at 3 years after diagnosis showed negative anti-GAD and anti-IA2, but positive anti-ZnT8. The patient was advised to maintain his bodyweight and healthy behavior together with closely regular OPD follow-up.

Conclusion: Restored beta-cell function with completely insulin withdrawal in new-onset T1DM has been reported in very few cases which have some common factors as in our patient (low carbohydrate intake with regular exercise). Delaying autoimmune activity by reducing metabolic load in newly diagnosed T1DM might play a role in maintaining a honeymoon period and could lead to an innovative therapeutic option in new-onset T1DM.
Type 1 Diabetes Mellitus and Familial Hypokalemic Periodic Paralysis: A Management Dilemma
Authors: Khine Aye H , Hernandez Joel , Sohal Aalam , Yin Ngwe
Published: May 2021

Background: Familial hypokalemic periodic paralysis (FHPP) is a rare condition characterized by episodes of painless muscle weakness associated with hypokalemia. It can be precipitated by heavy exercise and high carbohydrate meals. There have been cases illustrating treatment options to decrease the frequency of episodic weakness. However, insulin use in patients with FHPP has not been well studied or documented in literature.

Clinical Case: A 21-year-old male with known FHPP (heterozygous positive CACNA1S R1239H mutation) presented with nausea, vomiting, abdominal pain, and profound weakness. He had 1/5 strength in his upper and lower extremities bilaterally on examination. He was found to be in diabetic ketoacidosis (DKA). Insulin drip was initiated per DKA protocol and eventually converted to subcutaneous insulin. He continued to be weak and persistently hypokalemic, requiring potassium replacement (200 mEq/day). He had been on acetazolamide as preventive treatment for FHPP. It was switched to spironolactone in efforts to better control his potassium levels. His strength improved gradually, and he recovered 5/5 strength in his upper and lower extremities bilaterally by day 3 of admission. His weakness did not acutely worsen after receiving subcutaneous insulin. Further testing revealed elevated glutamic acid decarboxylase (GAD) antibodies consistent with type 1 diabetes mellitus (T1DM). His serum potassium on discharge was 4.4 mEq/L. He was discharged with subcutaneous insulin, potassium chloride 40 mEq three times daily, and spironolactone 100 mg daily. After discharge, serum potassium levels remained stable and potassium requirement decreased significantly to 40 mEq once daily.

Conclusion: This case illustrates the management dilemma between an unusual combination of diseases. The balance of potassium levels between insulin use in T1DM and FHPP creates significant challenges. Fortunately, the use of subcutaneous insulin in this patient did not appear to trigger episodic weakness. Further studies of hypokalemic periodic paralysis are critical to the institution of appropriate therapy and prevention of symptoms in patients with these conditions. Careful replacement and monitoring of potassium is recommended as patients require high doses of potassium during acute episodes of flaccid paralysis, and requirement significantly decreases after an acute episode.
Irisin Precursor FNDC5 and Glycemic Control in Patients With Type 2 Diabetes
Authors: Lima Mágero Felipe Rodrigues , Vasconcellos Larissa Frazao , Frazão Larissa , Bandeira Francisco
Published: May 2021

Introduction: Irisin is a newly discovered myokine whose expression is induced by exercise and PGC1α. Studies have reported its action on adipose tissue cells, leading to their “browning,” and consequent increase in energy expenditure and thermogenesis. In the first description of this hormone, which is a product of cleavage of its precursor (protein 5 containing fibronectin type III domain), elevated irisin levels were associated with improved insulin sensitivity, weight reduction, and better glucose tolerance in animal models. Hence, studies have tried to characterize the role of irisin in glucose regulation, with controversial results. Muscle mass has been a good predictor of irisin circulation in humans and, because it is predominantly synthesized and secreted by skeletal muscle, its use as a potential biomarker of sarcopenia has been investigated. Methods: The aim of this study was to evaluate serum FNDC5 levels according to clinical and metabolic parameters as well as muscle mass from patients with type 2 diabetes (T2DM). Body composition was evaluated by Dual X-ray absortptiometry (DXA) and multifrequency Bioelectric Impedance (BIA) and FNDC5 was measured using an ELISA kit. Results: We evaluated 44 women with type-2 diabetes, mean age of 61.95±8.52 years, mean diabetes duration of 10.25±7.06 years, mean HbA1c of 7.66±1.37, mean fasting plasma glucose of 149.11±38.26 mg/dL, mean BMI of 29.20±5.15 kg/m2, and mean abdominal circumference of 95.02±12.80 cm. Mean FNDC5/irisin was 18.69±3.67 ng/mL. Although there were no differences in DXA and BIA analyses according to first and top quartiles of serum FNDC5, we identified a negative correlation of serum FNDC5 with fasting plasma glucose (−0.479; P=0.001) and a positive correlation with age (0.422; P=0.004). Conclusion: our data demonstrated that increased serum FNDC5 is related to increased age and poor glycemic control in T2DM.

Reference: (1) Perakakis N et al., Physiology and role of irisin in glucose homeostasis. Nat Rev Endocrinol. 2017 (2) Hyun HP et al., The novel myokine irisin:clinical implications and potential role as a biomarker for sarcopenia in postmenopausal women. Endocrine. 2018.
Online CME Successful at Improving Awareness, Understanding, and Clinical Use of T2D Treatments
Authors: Larkin Amy , Le Anne
Published: May 2021

We sought to determine if an online continuing medical education (CME) curriculum could improve the clinical knowledge and competence of endocrinologists and primary care physicians (PCPs) related to knowledge and clinical use of GLP-1 RAs. The online CME curriculum consisted of 3 text- or video-based activities focused on practical tips for utilizing GLP-1 RAs in practice, benefits of GLP-1 RAs over therapeutic classes, and knowledge of oral GLP-1 RAs. The educational effects were assessed using a repeated pre-assessment/post-assessment study design. For all questions combined, a chi-squared test assessed whether the mean post-assessment score differed from the mean pre-assessment score (absolute changes reported). P values <.05 are statistically significant. The activities launched between June-August, 2019 and outcomes data were collected through November 2019. After being online and accredited for 1 year, the 3 activities have reached over 15,000 clinicians, over 9,500 of which were physicians. Improved knowledge and competence was demonstrated among the target audiences: • 13% increase in endocrinologists (P<.001) and PCPs (P<.001) who effectively utilized a GLP-1 RA in a practical scenario (competence) • 24% increase in endocrinologists (P<.001) and 21% increase in PCPs (P<.001) who identified the impact of GLP-RA therapy on cardiovascular outcomes (knowledge) • 17% increase in endocrinologists (P<.001) and 14% increase in PCPs (P<.001) who correctly identified cardiovascular impact of an emerging GLP-1 RA (knowledge) Persistent knowledge/competence gaps remain: • 9% of endocrinologists and 38% of PCPs need additional education to improve competence related to clinical use of GLP-1s in practice • 64% of endocrinologists and 62% of PCPs need additional education to improve knowledge on the impact of GLP-1 RAs on cardiovascular outcomes • 64% of endocrinologists and 74% of PCPs need additional education to improve knowledge on the cardiovascular impact of emerging GLP-1 RAs This study demonstrates the success of an online curriculum at improving knowledge and competence of endocrinologists and PCPs related to knowledge and clinical use of GLP-1 RAs. Persistent gaps were identified for future educational targets.
Trends in Medication Utilization and Glycemic Control Among Type 2 Diabetes Using a Common Data Model Based on Electronic Health Records From 2000 to 2019
Authors: Lee Kyung Ae , Jin Heung Yong , Jeong Seung Han , Kim Jang Hyeon , Kim Yuji , Park Tae Sun
Published: May 2021

Analyzing the treatment patterns of type 2 diabetes (T2DM) in real practice helps to understand the flow of diabetes management and establish further management plans. Observational Health Data Sciences and Informatics (OHDSI) is an international collaboration created an international data network (Observational Medical Outcomes Partnership Common Data Model, OMOP-CDM). This study was aim to analyze treatment patterns of T2DM using the OMOP-CDM based on electronic health record (EHR) data and to assess whether CDM analysis was feasible to diabetes research. This is a retrospective, observational study using the EHR data of Jeonbuk National University Hospital (JNUH) transformed into OMOP-CDM. The data consisted of medical records of patients visits from January 2000 to December 2019. ATLAS ver. 2.7.6, an OHDSI’s open-source software is publicly available, was used for analysis. The 20 year old EHR data of a JNUH contain about 1.5 million patients. The proportion of adult patients treated for T2DM increased from 1,867 (1.6%) in 2000 to 9,972 (5.1%) in 2019. Sulfonylurea (SU) was the most prescribed drug (73%) followed by metformin (55%) in 2000. On the other hand, in 2019, metformin was the most prescribed (64%), and DPP-4 inhibitor prescription increased rapidly up to 55%, while the SU prescription rate decreased to 36%. The rate of insulin treatment ranged from 16% to 24%, which is higher than national surveyed based on health insurance data. Over time, monotherapy decreased while dual, triple, and quadruple combinations steadily increased. Dual combination was the most common with metformin and DPP-4 inhibitor, triple combination was the most with metformin, SU, and DPP-4 inhibitor in 2019. In analysis of annual HbA1c trends, the proportion of patients with HbA1c of 7% or lower increased (from 32.8% 2000 to 50.2% in 2019). Proportion of patients with HbA1c of 9% or more decreased from 30% to 12%. However, it was found that about half of T2DM patients still had HbA1c values above the target range. In addition, the number of patients who visited our emergency room for severe hypoglycemia did not decrease. Present study revealed that CDM analysis was feasible for diabetes research. Medication utilization patterns have changed significantly over the past 20 years with a shift towards newer drugs. Despite these changes and clinical efforts, improvement in glycemic control is still a challenge and hypoglycemic is still a problem to overcome.
Efficacy and Safety of TLANDO, A Novel Oral Easy to Prescribe and Use TRT Option
Authors: Papangkorn Kongnara , Vangara Kiran , Bruno Benjamin J , Kim Kilyoung , Chidambaram Nachiappan , DelConte Anthony , Patel Mahesh , Carson III Culley C , Goldstein Irwin , Kaminetsky Jed , Miner Martin , Khera Mohit , Dobs Adrian Sandra
Published: May 2021

Most widely used testosterone replacement therapy (TRT) products can be inconvenient and cumbersome topical and invasive injectable requiring dose adjustments to attain efficacy. In a pivotal study, a recently approved oral TRT only 26% of patients did not require any dose adjustment. Typically, patients start on a sub-therapeutic dose with gradual dose increases to attain efficacy resulting in additional visit(s) to clinic and pharmacy. Physician research data (N=402) suggested it typically takes 3-6 months of titrations to reach an efficacious dose for majority of patients, a significant barrier in effecting a switch without a period of “efficacy gap”. The requirement of additional visit(s) presents significant challenges for new and current patients desiring to start and to switch to a convenient TRT option, especially in the current COVID-19 pandemic. Recent reports suggest increase of disease severity/mortality in men with low testosterone is possibly due to underlying co-morbidities commonly associated with male hypogonadism. There remains a need for an effective, safe, and easy to use and prescribe product that does not require dose titration. TLANDO is a “triglyceride-free” oral single strength TRT with single dose designed to lymphatically deliver effective and safe levels of testosterone regardless of meal fat content. Moreover, dose titration is prone to some inherent titration decision errors and requires understanding of often complex titration rules. The objective is to assess whether TLANDO, an oral TRT without requiring dose titration, safely restores effective testosterone (T) levels in hypogonadal men. An open-label, single-arm, multicenter study (NCT03242590) was performed with TLANDO in hypogonadal males (N=95). Subjects received orally 225 mg twice a day testosterone undecanoate (TU) for 24 days without dose adjustment. Efficacy was evaluated by % of subjects who achieved daily T Cavg within the eugonadal range. Using 450mg daily dose without dose adjustment, 80% of subjects (95% CI of 72% to 88%) achieved a T Cavg in the normal range and safely restored with mean T Cavg of 476±184 ng/dL post steady state. T restoration was comparable to other non-oral TRT products. TLANDO was well tolerated with no deaths, no drug-related severe AEs, and no hepatic AEs. In conclusion, effective T restoration using TLANDO, an easy to use and prescribe oral TRT option, was confirmed. Minimal AEs were reported with no hepatic AEs. Upon approval, TLANDO will be the first convenient TRT option without requiring dose adjustments; therefore, enabling selection of an efficacious dose from the start of therapy. TLANDO is well suited for new or existing TRT patients desiring a convenient oral option.
Thermoregulatory Responses with Size-matched Simulated Torso or Limb Skin Grafts
Authors: CRAMER MATTHEW N. , HUANG MU , FISCHER MADS , MORALEZ GILBERT , CRANDALL CRAIG G.
Published: May 2021

Skin grafting after a burn injury attenuates/abolishes sweat production within grafted areas. It is presently unknown whether the thermoregulatory consequences of skin grafting depend on anatomical location.

Purpose

This study aimed to test the hypothesis that a simulated burn injury on the torso will be no more or less detrimental to core temperature control than on the limbs during uncompensable exercise-heat stress.

Methods

Nine nonburned individuals (7 men, 2 women) completed the protocol. On separate occasions, burn injuries of identical surface area (0.45 ± 0.08 m2 or 24.4% ± 4.4% of total body surface area) were simulated on the torso or the arms/legs using an absorbent, vapor-impermeable material that impedes sweat evaporation in those regions. Participants performed 60 min of treadmill walking at 5.3 km·h−1 and a 4.1% ± 0.8% grade, targeting 6 W·kg−1 of metabolic heat production in 40.1°C ± 0.2°C and 19.6% ± 0.6% relative humidity conditions. Rectal temperature, heart rate, and perceptual responses were measured.

Results

Rectal temperature increased to a similar extent with simulated injuries on the torso and limbs (condition-by-time interaction, P = 0.86), with a final rectal temperature 0.9°C ± 0.3°C above baseline in both conditions. No differences in heart rate, perceived exertion, or thermal sensation were observed between conditions (condition-by-time interactions, P ≥ 0.50).

Conclusions

During uncompensable exercise-heat stress, sized-matched simulated burn injuries on the torso or limbs evoke comparable core temperature, heart rate, and perceptual responses, suggesting that the risk of exertional heat illness in such environmental conditions is independent of injury location.
LGBTQ Economics
Authors: Badgett M.V. Lee , Carpenter Christopher S. , Sansone Dario
Published: May 2021

Public attitudes and policies toward LGBTQ individuals have improved substantially in recent decades. Economists are actively shaping the discourse around these policies and contributing to our understanding of the economic lives of LGBTQ individuals. In this paper, we present the most up-to-date estimates of the size, location, demographic characteristics, and family structures of LGBTQ individuals in the United States. We describe an emerging literature on the effects of legal access to same-sex marriage on family and socioeconomic outcomes. We also summarize what is known about the size, direction, and sources of wage differentials related to variation in sexual orientation and gender identity. We conclude by describing a range of open questions in LGBTQ economics.
Por uma visão não demonizada do Estado pelo direito administrativo
Authors: Scodeler de Souza Barreiro Guilherme , Clark Giovani , Santana de Lelis Davi Augusto
Published: May 2021

O objeto do estudo é analisar algumas transformações do direito administrativo a partir da categoria proposta pelo professor Washington Peluso Albino de Souza, denominada ideologia constitucionalmente adotada, buscando responder ao seguinte questionamento: as mudanças sofridas pelo direito administrativo, após a promulgação da Constituição brasileira de 1988, se coadunam com a ideologia constitucionalmente adotada? Partimos da premissa de que os acadêmicos e políticos que propugnam alterações no direito administrativo são orientados por uma matriz neoliberal de regulação, ligada à reforma gerencial do Estado, e por conhecimentos arraigados à visão de demonização do Estado, ignorando, geralmente, os comandos dirigentes do texto constitucional brasileiro. Ademais, a pesquisa é bibliográfica e documental, apoiada na categoria ideologia constitucionalmente adotada, do saudoso jurista mineiro Washington Peluso Albino de Souza.
Dimensão social da sustentabilidade e a pandemia da Covid-19: uma análise das desigualdades sociais
Authors: Schmitt Siqueira Garcia Denise , Siqueira Garcia Heloise , Cruz Paulo Márcio
Published: May 2021

Covid-19 é o nome dado à doença causada pelo novo coronavírus que tem assustado a população global, não apenas por sua letalidade, mas essencialmente por sua velocidade de disseminação. O novo coronavírus ultrapassou rapidamente as fronteiras dos países de forma nunca vista, tornando-se um problema global em pouquíssimo tempo, evidenciando, com isso, a existência de problemas sociais e econômicos para a população. Como estamos vivendo o surto atualmente, não temos ainda uma noção precisa de sua real dimensão. Diante disso, o presente estudo é desenvolvido com o objetivo de analisar se a pandemia da Covid-19 aumentou as desigualdades sociais e consequentemente impactou a dimensão social da sustentabilidade. A metodologia utilizada baseia-se no método indutivo.
СРАВНИТЕЛЬНЫЙ АНАЛИЗ ВЛИЯНИЯ ЭКЗАМЕНАЦИОННОГО СТРЕССА НА УРОВЕНЬ СИТУАТИВНОЙ И ЛИЧНОСТНОЙ ТРЕВОЖНОСТИ СТУДЕНТОВ
Authors: Rustamova Tukazban V.
Published: May 2021

Цель. Изучение влияния экзаменационного процесса на изменения уровня ситуативной тревожности (УСТ) и уровня личностной тревожности (УЛТ) у студентов первого и пятого курсов в возрасте 17-21 года, относящихся к меланхолическому типу темперамента, в сравнении с сангвиниками, холериками и флегматиками.

Материалы и методы. Влияние эмоционального стресса на уровень ситуативной и личностной тревожности в трех различных ситуациях определялся экспресс версией тест-анкет по системе баллов: в обычные дни за два месяца до экзаменов (ОД), за 30 минут до экзамена (ДЭ) и через 30 минут после экзаменов (ПЭ).

Результаты и обсуждение. Установлено, что на всех этапах у студентов первого и пятого курсов уровень ситуативной и личностной тревожности между типами заметно отличается. У 17-летних студентов  (I курс) меланхолического типа экзаменационный стресс перед экзаменом и после экзаменов повышает УСТ по сравнению с ОД. У этих студентов от влияния экзаменационного стресса по сравнению с ОД, в периоды ДЭ и ПЭ показатели УЛТ повышаются практически на одинаковом уровне. У 21- летних студентов меланхолического типа под воздействием экзаменационного стресса по сравнению с ОД в периоды ДЭ и ПЭ УСТ повышается. У этих студентов экзаменационный стресс в период ДЭ и ПЭ по сравнению с ОД повышает УЛТ еще более выраженно.

Выводы. У 21-летних студентов (V курс) меланхолического типа экзаменационный стресс повышает УСТ и УЛТ более выраженно по сравнению с 17-летними (I курс). В разном возрасте и в условиях эмоционального напряжения экзамена, с помощью психофизиологического тестирования студентов разных курсов рекомендуется определять тип темперамента и разных форм уровней тревожности.
Digital health innovation to support sensitive enquiry about female genital mutilation
Authors: McEwan Joanne , Bedford Helen
Published: May 2021

Health professionals working in community settings are increasingly using mobile technologies to access information and support clients. A Mary Seacole Leadership Award enabled the production of an app, ‘Let's talk FGM’ (later becoming the web app letstalkfgm.nhs.uk ), to assist health professionals to make sensitive inquiry about female genital mutilation (FGM). This article outlines the rationale for the project and the steps needed for successful app development. It illustrates how clinical practitioners can respond to service users' needs, and in collaboration with colleagues and community groups, create responsive, usable tools which harness digital technology. It also showcases the role of partnership working and networking to develop the skills needed to lead within digital health.
Part 2: a qualitative description of participation in an eight-week infant skin integrity study
Authors: Phipps Fiona MacVane , Price Alan D , Ackers-Johnson James , Cook Penny A , Lythgoe Jeanne
Published: May 2021

Background

This is the second paper in a two-part series; the first paper was published in volume 29, issue 4 of the British Journal of Midwifery. The qualitative phase of the Baby Skin Integrity Comparison Survey (BaSICS) study was designed to address a dearth of information about research recruitment and retention, and how mothers make decisions about neonatal skincare.

Aims

The aim of the qualitative phase of the BaSICS study was to explore participants’ experience of participating in the research and how this interrelated with the experience of newborn skincare.

Methods

Semi-structured, face-to-face or telephone interviews were used to collect data. Interviews were transcribed verbatim. Data analysis used both software and manual methods.

Findings

Motivation included both altruism and personal benefits. The bespoke smartphone application was a convenient and easy tool for data collection, and being afforded full responsibility for observing and recording infant skin condition increased mothers' awareness of skin changes. Family, friends and the internet were the most commonly used sources of information about baby skincare.

Conclusion

The qualitative interview component of the BaSICS study provided information that could not have been deduced from the daily survey and final questionnaire alone. This provides valuable guidance for future research in the field of infant skincare.
Optical system for monitoring groundwater pressure and temperature using fiber Bragg gratings
Authors: Ho Yen-Te , Wang Yu-Li , Chang Liang-Cheng , Wang Tzu-Pin , Tsai Jui-Pin
Published: May 2021

A depth-discrete groundwater monitoring well is crucial to observing groundwater contamination and subsurface environments. To address this issue, we developed a multilevel monitoring system (MLMS). Because optical fiber sensors are small, have low voltage requirements, and have minimal signal loss over a long distance, we used fiber Bragg grating (FBG) technology to develop a MLMS to observe the depth-discrete aquifer status. The developed FBG sensors and MLMS were examined by a laboratory test and two field tests, respectively. The results show that the FBG piezometer and thermometer accuracies are 0.2% and 0.4% full-scale, respectively. The MLMS can be easily installed in a 2-inch well without a sealing process and can successfully measure the depth-discrete aquifer status at the selected fully-penetrated wells during the two injection events at the study site. The analysis of the collected data and their corresponding injection event reveals the possible structure of the subsurface hydraulic connections at the study sites. These results demonstrate that the FBG MLMS can be an alternative subsurface monitoring system, which has the advantage of a relatively low cost, good data collection efficiency, and environmental sustainability.
Multimode LD-pumped all-fiber Raman laser with excellent quality of 2nd-order Stokes output beam at 1019 nm
Authors: Kuznetsov A. G. , Nemov I. N. , Wolf A. A. , Kablukov S. I. , Babin S. A.
Published: May 2021

A multimode all-fiber Raman laser enabling cascaded generation of high-quality 1019-nm output beam at direct pumping by highly-multimode (M2>30) 940-nm laser diodes has been demonstrated. The laser is made of a 100/140 graded-index fiber with special in-fiber Bragg gratings which secure sequential generation of the 1st (976 nm) and 2nd (1019 nm) Stokes orders. Comparing different 1019-nm cavity structures shows that the half-open cavity with one FBG and distributed feedback via random Rayleigh backscattering provides excellent quality (M2∼1.3) with higher slope efficiency of pump-to-2nd Stokes conversion than in the conventional 2-FBG cavity. The maximum achieved slope efficiency amounts to about 40% at output powers of up to 12 W limited by the 3rd Stokes generation.
High sensitivity and large measurable range distributed acoustic sensing with Rayleigh-enhanced fiber
Authors: Xiong Ji , Wang Zinan , Jiang Jialin , Han Bing , Rao Yunjiang
Published: May 2021

In this Letter, high sensitivity and large measurable range distributed acoustic sensing (DAS) based on sub-chirped-pulse extraction algorithm (SPEA) in time domain and dechirp operation is proposed; moreover, Rayleigh-enhanced fiber is used to further improve the quality of Rayleigh scattering (RS) signal. In the proof-of-concept experiment, the RS pattern with 60 µɛ strain range is generated during a single-shot measurement, while

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z

strain sensitivity and 28.4 cm spatial resolution are achieved on 920 m fiber.
Millimeter-wave radio-over-fiber system using optical phase modulation and photonic downconversion for uplink fronthaul transmission
Authors: Tien Dat Pham , Yamaguchi Yuya , Kanno Atsushi , Motoya Masayuki , Oikawa Satoshi , Ichikawa Junichiro , Yamamoto Naokatsu
Published: May 2021

This Letter proposes a high-performance radio-over-fiber (RoF) system
for high-speed and high-fidelity analog waveform transmission of radio
signals in the millimeter-wave band in the uplink direction. At the
antenna site, the system utilizes a newly fabricated low half-wave
voltage broadband phase modulator to convert a millimeter-wave radio
signal into an optical signal. At the receiver, by using photonic
downconversion and optical filtering technology, a simple direct
detection and downconversion of the signal to the microwave band can
be achieved simultaneously. As a demonstration of proof of concept, we
successfully transmitted a 1024-quadrature amplitude modulation (QAM)
narrowband orthogonal frequency-division multiplexing signal at 38 GHz
and a 60 Gb/s 64-QAM single-carrier signal at 26.5 GHz over a 20 km
RoF system. The system is promising for facilitating the deployment of
ultra-dense small cells in high-frequency bands in 5G and
beyond networks.
Numerical analysis of the impact of cytoskeletal actin filament density alterations onto the diffusive vesicle-mediated cell transport
Authors: Haspinger Daniel Ch. , Klinge Sandra , Holzapfel Gerhard A.
Published: May 2021

The interior of a eukaryotic cell is a highly complex composite material which consists of water, structural scaffoldings, organelles, and various biomolecular solutes. All these components serve as obstacles that impede the motion of vesicles. Hence, it is hypothesized that any alteration of the cytoskeletal network may directly impact or even disrupt the vesicle transport. A disruption of the vesicle-mediated cell transport is thought to contribute to several severe diseases and disorders, such as diabetes, Parkinson’s and Alzheimer’s disease, emphasizing the clinical relevance. To address the outlined objective, a multiscale finite element model of the diffusive vesicle transport is proposed on the basis of the concept of homogenization, owed to the complexity of the cytoskeletal network. In order to study the microscopic effects of specific nanoscopic actin filament network alterations onto the vesicle transport, a parametrized three-dimensional geometrical model of the actin filament network was generated on the basis of experimentally observed filament densities and network geometries in an adenocarcinomic human alveolar basal epithelial cell. Numerical analyzes of the obtained effective diffusion properties within two-dimensional sampling domains of the whole cell model revealed that the computed homogenized diffusion coefficients can be predicted statistically accurate by a simple two-parameter power law as soon as the inaccessible area fraction, due to the obstacle geometries and the finite size of the vesicles, is known. This relationship, in turn, leads to a massive reduction in computation time and allows to study the impact of a variety of different cytoskeletal alterations onto the vesicle transport. Hence, the numerical simulations predicted a 35% increase in transport time due to a uniformly distributed four-fold increase of the total filament amount. On the other hand, a hypothetically reduced expression of filament cross-linking proteins led to sparser filament networks and, thus, a speed up of the vesicle transport.
Small subpopulations of β-cells do not drive islet oscillatory [Ca2+] dynamics via gap junction communication
Authors: Dwulet JaeAnn M. , Briggs Jennifer K. , Benninger Richard K. P.
Published: May 2021

The islets of Langerhans exist as multicellular networks that regulate blood glucose levels. The majority of cells in the islet are excitable, insulin-producing β-cells that are electrically coupled via gap junction channels. β-cells are known to display heterogeneous functionality. However, due to gap junction coupling, β-cells show coordinated [Ca2+] oscillations when stimulated with glucose, and global quiescence when unstimulated. Small subpopulations of highly functional β-cells have been suggested to control [Ca2+] dynamics across the islet. When these populations were targeted by optogenetic silencing or photoablation, [Ca2+] dynamics across the islet were largely disrupted. In this study, we investigated the theoretical basis of these experiments and how small populations can disproportionality control islet [Ca2+] dynamics. Using a multicellular islet model, we generated normal, skewed or bimodal distributions of β-cell heterogeneity. We examined how islet [Ca2+] dynamics were disrupted when cells were targeted via hyperpolarization or populations were removed; to mimic optogenetic silencing or photoablation, respectively. Targeted cell populations were chosen based on characteristics linked to functional subpopulation, including metabolic rate of glucose oxidation or [Ca2+] oscillation frequency. Islets were susceptible to marked suppression of [Ca2+] when ~10% of cells with high metabolic activity were hyperpolarized; where hyperpolarizing cells with normal metabolic activity had little effect. However, when highly metabolic cells were removed from the model, [Ca2+] oscillations remained. Similarly, when ~10% of cells with either the highest frequency or earliest elevations in [Ca2+] were removed from the islet, the [Ca2+] oscillation frequency remained largely unchanged. Overall, these results indicate small populations of β-cells with either increased metabolic activity or increased frequency are unable to disproportionately control islet-wide [Ca2+] via gap junction coupling. Therefore, we need to reconsider the physiological basis for such small β-cell populations or the mechanism by which they may be acting to control normal islet function.
Tranexamic acid and bleeding in patients treated with non-vitamin K oral anticoagulants undergoing dental extraction: The EXTRACT-NOAC randomized clinical trial
Authors: Ockerman Anna , Miclotte Isabel , Vanhaverbeke Maarten , Vanassche Thomas , Belmans Ann , Vanhove Jan , Meyns Joeri , Nadjmi Nasser , Van Hemelen Geert , Winderickx Patrick , Jacobs Reinhilde , Politis Constantinus , Verhamme Peter
Published: May 2021

Background

Oral bleeding after dental extraction in patients on non-vitamin K oral anticoagulants (NOACs) is a frequent problem. We investigated whether 10% tranexamic acid (TXA) mouthwash decreases post-extraction bleeding in patients treated with NOACs.

Methods and findings

The EXTRACT-NOAC study is a randomized, double-blind, placebo-controlled, multicenter, clinical trial. Patients were randomly assigned to 10% TXA or placebo mouthwash and were instructed to use the mouthwash once prior to dental extraction, and thereafter for 3 times a day for 3 days. The primary outcome was the number of patients with any post-extraction oral bleeding up to day 7. Secondary outcomes included periprocedural, early, and delayed bleeding, and the safety outcomes included all thrombotic events. The first patient was randomized on February 9, 2018 and the last patient on March 12, 2020. Of 222 randomized patients, 218 patients were included in the full analysis set, of which 106 patients were assigned to TXA (74.8 (±8.8) years; 81 men) and 112 to placebo (72.7 (±10.7) years; 64 men). Post-extraction bleeding occurred in 28 (26.4%) patients in the TXA group and in 32 (28.6%) patients in the placebo group (relative risk, 0.92; 95% confidence interval [CI], 0.60 to 1.42; P = 0.72). There were 46 bleeds in the TXA group and 85 bleeds in the placebo group (rate ratio, 0.57; 95% CI, 0.31 to 1.05; P = 0.07). TXA did not reduce the rate of periprocedural bleeding (bleeding score 4 ± 1.78 versus 4 ± 1.82, P = 0.80) and early bleeding (rate ratio, 0.76; 95% CI, 0.42 to 1.37). Delayed bleeding (rate ratio, 0.32; 95% CI, 0.12 to 0.89) and bleeding after multiple extractions (rate ratio, 0.40; 95% CI, 0.20 to 0.78) were lower in the TXA group. One patient in the placebo group had a transient ischemic attack while interrupting the NOAC therapy in preparation for the dental extraction. Two of the study limitations were the premature interruption of the trial following a futility analysis and the assessment of the patients’ compliance that was based on self-reported information during follow-up.

Conclusions

In patients on NOACs undergoing dental extraction, TXA does not seem to reduce the rate of periprocedural or early postoperative oral bleeding compared to placebo. TXA appears to reduce delayed bleeds and postoperative oral bleeding if multiple teeth are extracted.

Trial registration

ClinicalTrials.gov NCT03413891

EudraCT; EudraCT number:2017-001426-17; EudraCT Public website: eudract.ema.europa.eu.
Effects of exogenous β-glucanase on ileal digesta soluble β-glucan molecular weight, digestive tract characteristics, and performance of coccidiosis vaccinated broiler chickens fed hulless barley-based diets with and without medication
Authors: Karunaratne Namalika D. , Newkirk Rex W. , Ames Nancy P. , Van Kessel Andrew G. , Bedford Michael R. , Classen Henry L.
Published: May 2021

Introduction

Limited use of medication in poultry feed led to the investigation of exogenous enzymes as antibiotic alternatives for controlling enteric disease. The objective of this study was to evaluate the effects of diet β-glucanase (BGase) and medication on β-glucan depolymerization, digestive tract characteristics, and growth performance of broilers.

Materials and methods

Broilers were fed hulless barley (HB) based diets with BGase (Econase GT 200P from AB Vista; 0 and 0.1%) and medication (Bacitracin and Salinomycin Na; with and without) arranged as a 2 × 2 factorial. In Experiment 1, 160 broilers were housed in cages from d 0 to 28. Each treatment was assigned to 10 cages. In Experiment 2, broilers (2376) were housed in floor pens and vaccinated for coccidiosis on d 5. Each treatment was assigned to one floor pen in each of nine rooms.

Results

In Experiment 1, the soluble β-glucan weighted average molecular weight (Mw) in the ileal digesta was lower with medication in the 0% BGase treatments. Peak molecular weight (Mp) and Mw were lower with BGase regardless of medication. The maximum molecular weight for the smallest 10% β-glucan (MW-10%) was lower with BGase addition. In Experiment 2, Mp was lower with medication in 0% BGase treatments. Beta-glucanase resulted in lower Mp regardless of medication, and the degree of response was lower with medication. The MW-10% was lower with BGase despite antibiotic addition. Body weight gain and feed efficiency were higher with medication regardless of BGase use through-out the trial (except d 11–22 feed efficiency). Beta-glucanase resulted in higher body weight gain after d 11 and worsened and improved feed efficiency before and after d 11, respectively, in unmedicated treatments.

Conclusion

BGase and medication caused the depolymerization of soluble ileal β-glucan. Beta-glucanase acted as a partial replacement for diet medication by increasing growth performance in coccidiosis vaccinated broilers.
NF-kappa-B activation unveils the presence of inflammatory hotspots in human gut xenografts
Authors: Nissim-Eliraz Einat , Nir Eilam , Marsiano Noga , Yagel Simcha , Shpigel Nahum Y.
Published: May 2021

The single-epithelial cell layer of the gut mucosa serves as an essential barrier between the host and luminal microflora and plays a major role in innate immunity against invading pathogens. Nuclear factor kB (NF-κB), a central component of the cellular signaling machinery, regulates immune response and inflammation. NF-κB proteins are activated by signaling pathways downstream to microbial recognition receptors and cytokines receptors. Highly regulated NF-κB activity in intestinal epithelial cells (IEC) is essential for normal gut homeostasis; dysregulated activity has been linked to a number of disease states, including inflammatory bowel diseases (IBD) such as Crohn’s Disease (CD). Our aim was to visualize and quantify spatial and temporal dynamics of NF-κB activity in steady state and inflamed human gut. Lentivirus technology was used to transduce the IEC of human gut xenografts in SCID mice with a NF-κB luminescence reporter system. NF-κB signaling was visualized and quantified using low resolution, intravital imaging of the whole body and high resolution, immunofluorescence microscopic imaging of the tissues. We show that NF-κB is activated in select subset of IEC with low “leaky” NF-κB activity. These unique inflammatory epithelial cells are clustered in the gut into discrete hotspots of NF-κB activity that are visible in steady state and selectively activated by systemic LPS and human TNFα or luminal bacteria. The presence of inflammatory hotspots in the normal and inflamed gut might explain the patchy mucosal lesions characterizing CD and thus could have important implications for diagnosis and therapy.
A systematic review of exercise testing in patients with intermittent claudication: A focus on test standardisation and reporting quality in randomised controlled trials of exercise interventions
Authors: Birkett Stefan T. , Harwood Amy E. , Caldow Edward , Ibeggazene Saïd , Ingle Lee , Pymer Sean
Published: May 2021

A systematic review was conducted to identify the range of terminology used in studies to describe maximum walking distance and the exercise testing protocols, and testing modalities used to measure it in patients with intermittent claudication. A secondary aim was to assess the implementation and reporting of the exercise testing protocols. CINAHL, Medline, EMBASE and Cochrane CENTRAL databases were searched. Randomised controlled trials whereby patients with intermittent claudication were randomised to an exercise intervention were included. The terminology used to describe maximal walking distance was recorded, as was the modality and protocol used to measure it. The implementation and reporting quality was also assessed using pre-specified criteria. Sixty-four trials were included in this review. Maximal walking distance was reported using fourteen different terminologies. Twenty-two different treadmill protocols and three different corridor tests were employed to assess maximal walking distance. No single trial satisfied all the implementation and reporting criteria for an exercise testing protocol. Evidence shows that between-study interpretation is difficult given the heterogenous nature of the exercise testing protocols, test endpoints and terminology used to describe maximal walking distance. This is further compounded by poor test reporting and implementation across studies. Comprehensive guidelines need to be provided to enable a standardised approach to exercise testing in patients with intermittent claudication.
Assessment of carbapenems in a mouse model of Mycobacterium tuberculosis infection
Authors: Jadhav Ravindra , Gallardo-Macias Ricardo , Kumar Gaurav , Daher Samer S. , Kaushik Amit , Bigelow Kristina M. , Nuermberger Eric L. , Lamichhane Gyanu , Freundlich Joel S.
Published: May 2021

We present further study of a subset of carbapenems, arising from a previously reported machine learning approach, with regard to their mouse pharmacokinetic profiling and subsequent study in a mouse model of sub-acute Mycobacterium tuberculosis infection. Pharmacokinetic metrics for such small molecules were compared to those for meropenem and biapenem, resulting in the selection of two carbapenems to be assessed for their ability to reduce M. tuberculosis bacterial loads in the lungs of infected mice. The original syntheses of these two carbapenems were optimized to provide multigram quantities of each compound. One of the two experimental carbapenems, JSF-2204, exhibited efficacy equivalent to that of meropenem, while both were inferior to rifampin. The lessons learned in this study point toward the need to further enhance the pharmacokinetic profiles of experimental carbapenems to positively impact in vivo efficacy performance.
Forest biomass carbon pool dynamics in Tibet Autonomous Region of China: Inventory data 1999-2019
Authors: Shu-Qin Liu , Zhen Bian , Chao-Zong Xia , Ahmad Bilal , Ming Zhang , Jian Chen , Tian-Yu An , Ke-Bin Zhang
Published: May 2021

According to the forest resources inventory data for different periods and the latest estimation parameters of forest carbon reserves in China, the carbon reserves and carbon density of forest biomass in the Tibet Autonomous Region from 1999 to 2019 were estimated using the IPCC international carbon reserves estimation model. The results showed that, during the past 20 years, the forest area, forest stock, and biomass carbon storage in Tibet have been steadily increasing, with an average annual increase of 1.85×104 hm2, 0.033×107 m3, and 0.22×107 t, respectively. Influenced by geographical conditions and the natural environment, the forest area and biomass carbon storage gradually increased from the northwest to the southeast, particularly in Linzhi and Changdu, where there are many primitive forests, which serve as important carbon sinks in Tibet. In terms of the composition of tree species, coniferous forests are dominant in Tibet, particularly those containing Abies fabri, Picea asperata, and Pinus densata, which comprise approximately 45% of the total forest area in Tibet. The ecological location of Tibet has resulted in the area being dominated by shelter forest, comprising 68.76% of the total area, 64.72% of the total forest stock, and 66.34% of the total biomass carbon reserves. The biomass carbon storage was observed to first increase and then decrease with increasing forest age, which is primarily caused by tree growth characteristics. In over-mature forests, trees’ photosynthesis decreases along with their accumulation of organic matter, and the trees can die. In addition, this study also observed that the proportion of mature and over-mature forest in Tibet is excessively large, which is not conducive to the sustainable development of forestry in the region. This problem should be addressed in future management and utilization activities.