bluuebunny/crossref_metadata_2025 huggingface dataset:
Cilostazol versus aspirin in ischemic stroke with cerebral microbleeds versus prior intracerebral hemorrhage
Authors: Park Hong-Kyun , Lee Ji Sung , Kim Bum Joon , Park Jong-Ho , Kim Yong-Jae , Yu Sungwook , Hwang Yang-Ha , Rha Joung-Ho , Heo Sung Hyuk , Ahn Seong Hwan , Seo Woo-Keun , Park Jong-Moo , Lee Ju-Hun , Kwon Jee-Hyun , Sohn Sung-Il , Jung Jin-Man , Kwon Sun U , Hong Keun-Sik ,   on behalf of the PICASSO investigators
Published: July 2020

Background

In PreventIon of CArdiovascular Events in Ischaemic Stroke Patients with High Risk of Cerebral HaemOrrhage (PICASSO), cilostazol versus aspirin was comparable for the end points of cerebral hemorrhage and major vascular events. However, underlying hemorrhage-prone lesions could modify the treatment effect.

Aims

We explored whether the safety and efficacy of cilostazol versus aspirin would differ between hemorrhage-prone lesions (multiple cerebral microbleeds vs. prior intracerebral hemorrhage).

Methods

In this post hoc analysis of PICASSO, we divided patients into the cerebral microbleeds and prior intracerebral hemorrhage subgroups. The primary safety end point was the first occurrence of cerebral hemorrhage. The primary efficacy end point was the composite of stroke, myocardial infarction, or vascular death.

Results

Of 1512 patients, 903 (59.7%) had multiple cerebral microbleeds and 609 (40.3%) had prior intracerebral hemorrhage. The cerebral hemorrhage risk was lower with cilostazol versus aspirin (0.12%/year vs. 1.49%/year; hazard ratio, 0.08 [95% confidence interval 0.01–0.60]; p = 0.015) in the cerebral microbleeds subgroup, but was not different (1.26%/year vs. 0.79%/year; hazards ratio 1.60 [0.52–4.90]; p = 0.408) in the prior intracerebral hemorrhage subgroup. The interaction of treatment-by-subgroup was significant ( pinteraction = 0.011). For the composite of major vascular events, there was a trend toward a lower risk with cilostazol versus aspirin (3.56%/year vs. 5.53%/year; hazards ratio 0.64 [0.41–1.01]; p = 0.056) in the cerebral microbleeds subgroup, but was comparable (5.21%/year vs. 5.05%/year; hazards ratio 1.03 [0.63–1.67]; p = 0.913) in the prior intracerebral hemorrhage subgroup without a significant treatment-by-subgroup interaction ( pinteraction = 0.165).

Conclusions

Cilostazol versus aspirin might be a better option in ischemic stroke with multiple cerebral microbleeds, but confirmatory trials are needed.

Clinical Trial Registration

URL: http://www.clinicaltrials.gov . NCT01013532.
Comparative risk of serious and fatal treatment-related adverse events caused by 19 immune checkpoint inhibitors used in cancer treatment: a network meta-analysis
Authors: Liu Tingting , Jin Bo , Chen Jun , Wang Hui , Lin Shuiyu , Dang Jun , Li Guang
Published: July 2020

Background:

This network meta-analysis assessed the comparative risk of grade 3–5 and grade 5 treatment-related adverse events (TRAEs) for immune checkpoint inhibitors (ICIs), either alone or in combination with other modalities, for cancer treatment.

Methods:

PubMed, Embase, Cochrane Library, Web of Science, and recent predominant oncology congresses were searched for relevant phase II and phase III randomized controlled trials (RCTs). As outcomes, grade 3–5, and grade 5 TRAE outcomes were reported as odds ratios and 95% confidence intervals.

Results:

In 67 RCTs involving 36,422 patients and 19 ICIs, the incidence of grade 3–5 and grade 5 TRAEs was 17.9% and 0.8% with ICI monotherapy and 46.3% and 1.4%, respectively, with combinatorial therapy. Pneumonitis was the most common cause of grade 5 TRAEs following either monotherapy (16.3%) or combinatorial therapy (11.4%). Regarding grade 3–5 TRAEs, atezolizumab + chemotherapy (CT) and antiangiogenic therapy (AT) (atezolizumab + CAT), pembrolizumab + CT, ipilimumab + CT, and atezolizumab + CT were more toxic than any ICI monotherapy, pembrolizumab or nivolumab + radiotherapy (RT), and ICIs dual therapy (durvalumab + tremelimumab and nivolumab + ipilimumab). Tremelimumab, ipilimumab, durvalumab, and pembrolizumab were, however, associated with higher grade 5 TRAEs than combinatorial treatments. Atezolizumab + CAT was the most toxic and nivolumab + RT was the least toxic of combinatorial treatments; among monotherapies, tremelimumab and avelumab were the most and least toxic, respectively. The toxicity ranking changed with type of grade 3–5 TRAEs.

Conclusions:

Compared with combinatorial therapy, ICI monotherapy caused lower grade 3–5 TRAEs, but some monotherapies resulted in a higher incidence of fatal TRAEs. Atezolizumab + CAT and nivolumab + RT were the most and least toxic of combinatorial treatments, respectively, and tremelimumab and avelumab were the most and least toxic of the monotherapies, respectively.
Disabled Students Seeking Higher Education in Kashmir: A Study of their Experiences
Authors: Khan Tanveer Ahmad , Hamid Wasia , Jahangir Mohmad Saleem , Maqbool Tabbasum
Published: July 2020

The present study aimed to understand the experiences of disabled students while gaining higher education in Kashmir. According to the conference on the ‘Rights of Persons with Disability’, Article 24, 2(a), disabled persons should not be barred from broader education organizations due to their disability. Besides, the ‘Millennium Development Goals’ and ‘Education for All’ insist on justice, equality and quality education for all. Yet, like in other societies, in Kashmir too disabled people face a large number of obstacles while attempting to achieve higher education. The study was conducted on 21 disabled students studying at the University of Kashmir during the year 2018. The results revealed that disabled people face a large number of obstacles while accessing education and come across a vast amount of challenges such as experiencing harassment, being excluded from the university, lack of institutional support, accommodation, financial support, seminars and infrastructure and facilities necessary to obtain benefits from the equivalent quality of education as their colleague.
Three Decades of Progress in Sleep Disorders and Sleep Health for Women
Authors: Marsella Jennifer L. , Sharkey Katherine M.
Published: July 2020

Over the past 3 decades, significant strides have been made in the field of sleep medicine for women. The impact of sex and gender on sleep health and sleep disorders received little attention in the early 1990s, but driven by policies ensuring inclusion of women in medical research, more recent studies have identified sex differences in sleep and investigated gender differences in sleep disorders. Nevertheless, disparities remain: diagnosis of sleep disorders, such as obstructive sleep apnea, narcolepsy, and rapid eye movement (REM) sleep behavior disorder are often delayed and underdiagnosed in women. Future research should continue to examine how biological sex and identity across the gender spectrum influence sleep health and sleep disorders, allowing for more personalized health care for all patients.
Occupational benzene exposure and the risk of genetic damage: a systematic review and meta-analysis
Authors: Zhou Yanhua , Wang Kun , Wang Boshen , Pu Yuepu , Zhang Juan
Published: July 2020

Background

Benzene, an important component of organic solvents, is commonly used in industry. Meanwhile, benzene is a human carcinogen leading to leukemia. Although the links between benzene and various types of genetic damage indicators have been evaluated in several studies, but their results remain inconsistent. So we conducted a meta-analysis, and to explore the influence of low concentration benzene exposure on workers’ genetic damage indicators using 3.25 mg/m3 as the boundary value, in order to provide a basis for improved prevention and control of the harm from benzene exposure to the occupational population.

Methods

We conducted a search of five databases, including Pub Med, Web of Science, China National Knowledge Infrastructure (CNKI), Wan Fang Data and Chongqing VIP, to identify relevant articles up to December 25, 2018. Two researchers independently extracted and evaluated the data according to the inclusion and exclusion criteria of the literature. The imported articles were managed by Endnote X7, and the data were extracted and sorted by Excel 2013. We utilized Stata 12.0 software to perform the meta-analysis in the present study.

Results

A total of 68 eligible articles were finally included for the synthetic analyses. The meta-analysis results showed that occupational benzene exposure led to significantly increased Micronucleus (MN) frequency, Sister chromatid exchange (SCE) frequency, Chromosome aberration (CA) frequency, Olive Tail moment (OTM), Tail moment (TM), Tail length (TL), and Tail DNA% (T DNA%) compared to the control group (P < 0.05), and the pooled effect value estimates were 1.36, 0.98, 0.76, 1.06, 0.96, 1.78, and 1.42, respectively. Subsequent analysis of the effect of low concentration benzene exposure on genetic damage found significantly increased MN frequency increased compared with the control group (P < 0.05).

Conclusions

Occupational benzene exposure can affect multiple genetic damage indicators. Even at an exposure concentration lower than 3.25 mg/m3, benzene exposure has genotoxicity. These data provide an important scientific basis for the further revision of occupational disease prevention strategies. At the same time, increased attention should be focused on the health monitoring of the occupational population exposed to benzene, and health management should be strengthened to improve the health of the occupational population.
Traditional healers use of personal protective equipment: a qualitative study in rural South Africa
Authors: Audet Carolyn M. , Gobbo Elisa , Sack Daniel E. , Clemens Elise M. , Ngobeni Sizzy , Mkansi Mevian , Aliyu Muktar H. , Wagner Ryan G.
Published: July 2020

Background

Traditional healers are frequently exposed to hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) through the widespread practice of traditional “injections”, in which the healer performs dozens of subcutaneous incisions using a razor blade to rub herbs directly into bloodied tissue. An average healer in Agincourt, a rural northeastern sub-district in Mpumalanga province, South Africa, experiences approximately 1500 occupational blood exposures over the course of their lifetime. Healers in Agincourt have an HIV prevalence of 30% compared to 19% in the general population, and healers who report exposure to patient blood have an adjusted 2.4-fold higher odds of being HIV-positive than those with no exposure. Although research on appropriate PPE use has been well documented for allopathic care providers, little is known about the practices of traditional healers.

Methods

This qualitative study was conducted with 30 traditional healers who practice in the rural Bushbuckridge sub-district of Mpumalanga province, northeastern South Africa. We elicited traditional healer attitudes towards glove use during traditional treatments – including patient baths, injections, or other treatments that exposed healers to patient blood or open sores.

Results

While 90% of healers reported using latex gloves during some treatments, the majority do not use them regularly. Most employ a combination of gloves, plastic shopping bags, bread bags, paper, and sticks to prevent blood exposure. Healers reported plastic bags slipping or breaking during procedures, exposing them to patient blood. Only three healers consistently used gloves, regardless of the cost.

Conclusions

Inadequate PPE use and high HIV prevalence make traditional healers particularly susceptible to contracting HIV in rural South Africa. Despite positive attitudes, consistent glove use remains low due to financial constraints and glove availability. Addressing issues of accessibility and cost of gloves for traditional healers could have a significant impact on the adherence to PPE and, in turn, reduce new HIV infections among this high-risk group.
New insights into genetic susceptibility of COVID-19: an ACE2 and TMPRSS2 polymorphism analysis
Authors: Hou Yuan , Zhao Junfei , Martin William , Kallianpur Asha , Chung Mina K. , Jehi Lara , Sharifi Nima , Erzurum Serpil , Eng Charis , Cheng Feixiong
Published: July 2020

Background

Coronavirus Disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has now been confirmed worldwide. Yet, COVID-19 is strangely and tragically selective. Morbidity and mortality due to COVID19 rise dramatically with age and co-existing health conditions, including cancer and cardiovascular diseases. Human genetic factors may contribute to the extremely high transmissibility of SARS-CoV-2 and to the relentlessly progressive disease observed in a small but significant proportion of infected individuals, but these factors are largely unknown.

Main body

In this study, we investigated genetic susceptibility to COVID-19 by examining DNA polymorphisms in ACE2 and TMPRSS2 (two key host factors of SARS-CoV-2) from ~ 81,000 human genomes. We found unique genetic susceptibility across different populations in ACE2 and TMPRSS2. Specifically, ACE2 polymorphisms were found to be associated with cardiovascular and pulmonary conditions by altering the angiotensinogen-ACE2 interactions, such as p.Arg514Gly in the African/African-American population. Unique but prevalent polymorphisms (including p.Val160Met (rs12329760), an expression quantitative trait locus (eQTL)) in TMPRSS2, offer potential explanations for differential genetic susceptibility to COVID-19 as well as for risk factors, including those with cancer and the high-risk group of male patients. We further discussed that polymorphisms in ACE2 or TMPRSS2 could guide effective treatments (i.e., hydroxychloroquine and camostat) for COVID-19.

Conclusion

This study suggested that ACE2 or TMPRSS2 DNA polymorphisms were likely associated with genetic susceptibility of COVID-19, which calls for a human genetics initiative for fighting the COVID-19 pandemic.
Could hemophagocytic lymphohistiocytosis be the core issue of severe COVID-19 cases?
Authors: Opoka-Winiarska Violetta , Grywalska Ewelina , Roliński Jacek
Published: July 2020

Background

COVID-19, a disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly presents as fever, cough, dyspnea, and myalgia or fatigue. Although the majority of patients with COVID-19 have mild symptoms, some are more prone to serious outcomes, including pneumonia, acute respiratory distress syndrome (ARDS), and even death. Hemophagocytic lymphohistiocytosis (HLH) is a severe, life-threatening inflammatory syndrome associated with intense cytokine release (also known as a “cytokine storm”). Similar to COVID-19, HLH is characterized by aggressive course leading to multi-organ failure.

Main text

The purpose of this review article is to draw attention to the possibility of the complication of HLH in patients with the severe course of COVID-19. Indeed, some of the clinical characteristics observed in the more severe cases of COVID-19 are reminiscent of secondary HLH (which can be triggered by infections, malignancies, rheumatological diseases, or autoimmune/immunodeficiency conditions). The pathogenesis of SARS-CoV-2 infection also suggests that HLH or a similar hyperinflammatory syndrome is the cause of the severe course of the infection.

Conclusion

The pathogenesis and clinical symptoms of severe COVID-19 indicate that an increased inflammatory response corresponding to HLH is occurring. Therefore, patients with severe COVID-19 should be screened for hyperinflammation using standard laboratory tests to identify those for whom immunosuppressive therapy may improve outcomes.
Early epidemiological assessment of the transmission potential and virulence of coronavirus disease 2019 (COVID-19) in Wuhan City, China, January–February, 2020
Authors: Mizumoto Kenji , Kagaya Katsushi , Chowell Gerardo
Published: July 2020

Background

Since the first cluster of cases was identified in Wuhan City, China, in December 2019, coronavirus disease 2019 (COVID-19) rapidly spreads globally. Scientists have made strides in estimating key transmission and epidemiological parameters. In particular, accumulating evidence points to a substantial fraction of asymptomatic or subclinical infections, which influences our understanding of the transmission potential and severity of this emerging disease. In this study, we derive estimates of the transmissibility and virulence of COVID-19 in Wuhan City, China, by reconstructing the underlying transmission dynamics using multiple data sources.

Methods

We employ statistical methods and publicly available epidemiological datasets to jointly derive estimates of transmissibility and severity associated with the novel coronavirus. For this purpose, the daily series of laboratory-confirmed COVID-19 cases and deaths in Wuhan City together with epidemiological data of Japanese repatriated from Wuhan City on board government-chartered flights were integrated into our analysis.

Results

Our posterior estimates of basic reproduction number (R) in Wuhan City, China, in 2019–2020 reached values at 3.49 (95% CrI 3.39–3.62) with a mean serial interval of 6.0 days, and the enhanced public health intervention after January 23 in 2020 was associated with a significantly reduced R at 0.84 (95% CrI 0.81–0.88), with the total number of infections (i.e., cumulative infections) estimated at 1,906,634 (95% CrI 1,373,500–2,651,124) in Wuhan City, elevating the overall proportion of infected individuals to 19.1% (95% CrI 13.5–26.6%). We also estimated the most recent crude infection fatality ratio (IFR) and time–delay adjusted IFR at 0.04% (95% CrI 0.03–0.06%) and 0.12% (95% CrI 0.08–0.17%), respectively, estimates that are substantially smaller than the crude CFR estimated at 4.06%.

Conclusions

We have estimated key epidemiological parameters of the transmissibility and virulence of COVID-19 in Wuhan, China, during January–February 2020 using an ecological modeling approach that is suitable to infer epidemiological parameters with quantified uncertainty from partial observations collected by surveillance systems. Our estimate of time–delay adjusted IFR falls in the range of the median IFR estimates based on multiple serological studies conducted in several areas of the world.
Association between mild stimulated IVF/M cycle and early embryo arrest in sub fertile women with/without PCOS
Authors: Elshewy Nagwa , Ji Dongmei , Zhang Zhiguo , Chen Dawei , Chen Beili , Xue Rufeng , Wu Huan , Wang Jianye , Zhou Ping , Cao Yunxia
Published: July 2020

Background

The in vitro maturation (IVM) technique has physical and financial benefits, but a lower efficiency and outcome that is still unclear whether it is related to polycystic ovary syndrome (PCOS) itself or the IVM procedure. In this study, we analyzed the clinical and laboratory outcomes of an optimized IVM protocol in patients with and without PCOS. We also discussed the possible reasons for early embryo arrest in the IVM cycle.

Methods

This prospective study involved 58 PCOS patients and 56 non-PCOS patients who underwent mild stimulated IVF combined IVM (IVF/M) cycles. The clinical and laboratory outcomes were compared between the two groups. Also, metaphase II (MII) oocytes were obtained after IVM from the two groups, and in vivo MII oocytes randomly collected from IVF patients were examined for mitochondrial function using a laser scanning confocal microscope (LSCM). The aneuploidy rate for arrested cleavage embryos from IVM and IVF oocytes were screened using Next Generation Sequencing (NGS).

Results

Mildly stimulated IVF/M resulted in cumulative clinical pregnancy and implantation rates (40.2, 28.7% in the PCOS group vs. 41.9, 36% in the non-PCOS group), respectively. The blastocyst formation rates were comparable (28% vs. 28.2%) in PCOS and non-PCOS groups, respectively. Using LSCM, there was a significant decrease in the mitochondrial membrane potential of IVM oocytes compared with the control IVF oocytes (P < 0.001), but no significant difference between the PCOS and non-PCOS groups. The NGS showed that the aneuploidy rates were comparable (75, 75, and 66.6%) in IVM-PCOS, IVM-non-PCOS, and control IVF arrested embryos, respectively.

Conclusions

The mildly stimulated IVF/M protocol produced acceptable clinical outcomes in PCOS and non-PCOS patients. IVM itself rather than the PCOS condition adversely affected the embryo development through its effect on mitochondrial function, which appeared to be a possible cause for the embryo arrest in the IVM cycles rather than chromosomal aneuploidy.
Study on the outcome of patients with aseptic femoral head necrosis treated with percutaneous multiple small-diameter drilling core decompression: a retrospective cohort study based on magnetic resonance imaging and equivalent sphere model analysis
Authors: Tan Yang , He Hangyuan , Wan Zihao , Qin Jun , Wen Yinxian , Pan Zhengqi , Wang Hua , Chen Liaobin
Published: July 2020

Background

Aseptic necrosis of the femoral head (ANFH) has a high incidence in the community and causes substantial problems with health as well as economic and social stress. Core decompression is the most commonly used treatment for early ANFH. Although many studies have reported on the efficacy of femoral head core decompression surgery for ANFH, there are still some shortcomings in assessing the severity of femoral head necrosis, the location distribution, and changes in necrotic lesions before and after surgery. Magnetic resonance imaging (MRI) and equivalent sphere model analysis were used to further clarify the clinical efficacy of percutaneous multiple small-diameter drilling core decompression in patients with ANFH.

Methods

From July 2013 to November 2016, 24 patients (32 cases of the hip joint) with ANFH who underwent percutaneous multiple small-diameter drilling core decompression were selected, and a retrospective analysis was conducted. MRI as well as VAS, OHS-C, and HHS scores were used to evaluate joint function in all patients before and 6, 12, and 24 months after the operation.

Results

Twenty-four months after the operation, 10 hips were amputated. The survival rates of alcoholic femoral head necrosis (AFNH), idiopathic femoral head necrosis (IFHN), and steroid-induced femoral head necrosis (SIFHN) patients at 24 months were 100%, 85.7% (− 2 hips), and 0.0% (− 8 hips), respectively. The MRI and equivalent sphere analysis results revealed that the anterior superior medial quadrant was the area most prone to osteonecrosis, and the posterior superior medial quadrant was the area second most prone to necrosis. After the operation, the average percentage of the AFHN necrosis area in the total volume of the femoral head decreased from 14.5 to 10.3%, and the average percentage of the IFHN necrosis area decreased from 16.3 to 9.2%; however, the average percentage of the necrosis area for SIFHN increased from 30.4 to 33.1%.

Conclusion

Percutaneous multiple small-diameter drilling core decompression significantly reduced the lesion volume for AFHN and IFHN, but the effect on SIFHN was not good.
Adapting acute malnutrition treatment protocols in emergency contexts: a qualitative study of national decision-making
Authors: Kozuki Naoko , Seni Mamoudou , Sirat Amin , Abdullahi Omar , Adalbert Mena Fundi Eso , Biotteau Marie , Goldsmith Amelia , Dalglish Sarah L.
Published: July 2020

Background

Each year, an estimated 17 million children suffer from severe acute malnutrition (SAM) and 33 million from moderate acute malnutrition (MAM), with many of the most severe cases found in extremely food insecure contexts or conflict situations. Current global outpatient treatment protocols for uncomplicated SAM and MAM, adapted by most countries for use at national level, call for SAM and MAM to be managed separately, however global-level stakeholders have recently begun evaluating simplified and/or combined protocols managing acute malnutrition.

Methods

This study analyzes national policy discussions and decision-making around outpatient acute malnutrition treatment for uncomplicated cases in emergency situations in Niger, Nigeria, Somalia, and South Sudan. Data collection (March–July 2018) included semi-structured in-depth interviews with 50 respondents (N = 11–15 per country) from government, funding agencies, and implementing partners, as well as 11 global and regional stakeholders. We also conducted a document analysis (N = 10–15 per country and at global level) to situate debates and evaluate current policy. Data were analyzed iteratively using thematic content analysis.

Results

We find that while combined/simplified protocols for outpatient management of uncomplicated cases of acute malnutrition are being used in emergency situations in all four countries, there is widespread confusion about protocol terminology and content, stemming from a lack of coherence at the global level. As a result, national-level stakeholders express diverse, if overlapping, rationales for modifying current protocols, which vary given the intensity and scope of the emergency. Without specific global-level guidance, combined/simplified protocols are often used on an ad hoc basis, although the processes for triggering them were at least nominally controlled at the national level. Decisions about when and where to enact “exceptional” modifications to country protocols were often based on inconsistent determinations of what constitutes an “emergency.” Respondents said more evidence is needed on both clinical and operational aspects of these protocols, and they awaited clear guidance from global norm-setting agencies.

Conclusions

Based on these findings, global-level stakeholders should urgently improve coordination and communication around existing protocols. Standardized guidance based on the available evidence is required to clarify best practices for combined management of SAM and MAM, particularly in emergency contexts (which should be defined) and in situations of limited resources. Given the complexity of governance arrangements in conflict situations, both guidance and updates on research must be disseminated in a rational, systematic, and digestible way to the multiplicity of field actors.
Longitudinal changes in EEG power, sleep cycles and behaviour in a tau model of neurodegeneration
Authors: Holton C. M. , Hanley N. , Shanks E. , Oxley P. , McCarthy A. , Eastwood B. J. , Murray T. K. , Nickerson A. , Wafford K. A.
Published: July 2020

Background

Disturbed sleep is associated with cognitive decline in neurodegenerative diseases such as Alzheimer’s disease (AD) and frontotemporal dementia (FTD). The progressive sequence of how neurodegeneration affects aspects of sleep architecture in conjunction with behavioural changes is not well understood.

Methods

We investigated changes in sleep architecture, spectral power and circadian rhythmicity in the tet-off rTg4510 mouse overexpressing human P301L tau within the same subjects over time. Doxycycline-induced transgene-suppressed rTg4510 mice, tTa carriers and wild-type mice were used as comparators. Spectral power and sleep stages were measured from within the home cage environment using EEG electrodes. In addition, locomotor activity and performance during a T-maze task were measured.

Results

Spectral power in the delta and theta bands showed a time-dependent decrease in rTg4510 mice compared to all other groups. After the initial changes in spectral power, wake during the dark period increased whereas NREM and number of REM sleep bouts decreased in rTg4510 compared to wild-type mice. Home cage locomotor activity in the dark phase significantly increased in rTg4510 compared to wild-type mice by 40 weeks of age. Peak-to-peak circadian rhythm amplitude and performance in the T-maze was impaired throughout the experiment independent of time. At 46 weeks, rTG4510 mice had significant degeneration in the hippocampus and cortex whereas doxycycline-treated rTG4510 mice were protected. Pathology significantly correlated with sleep and EEG outcomes, in addition to locomotor and cognitive measures.

Conclusions

We show that reduced EEG spectral power precedes reductions in sleep and home cage locomotor activity in a mouse model of tauopathy. The data shows increasing mutant tau changes sleep architecture, EEG properties, behaviour and cognition, which suggest tau-related effects on sleep architecture in patients with neurodegenerative diseases.
Natural history, prognostic factors and patient perceived response to treatment in chronic spontaneous urticaria
Authors: Stepaniuk Peter , Kan Manstein , Kanani Amin
Published: July 2020

Background

Although the diagnosis and management of chronic spontaneous urticaria (CSU) is well documented in the literature, some aspects of the disease remain unclear. We aimed to further describe the natural history, prognostic factors, humanistic burden and uptake of traditional and alternative therapies in patients with CSU.

Methods

This was a prospective, cross-sectional analysis at a single centre. We reviewed patient medical records and conducted a survey in patients with CSU.

Results

72 patients participated in the study with a median duration of CSU of 48 months. 30% of patients had symptoms that resolved in under 2 years with these patients trending towards an older age of onset of CSU (48 ± 17 years). 16% of patients had symptoms lasting 10 years or longer with these patients trending towards a younger age of onset (22 ± 16 years). Patients with a relapsing/remitting disease course (31%) and those with co-existing angioedema (57%) trended towards a longer median duration of CSU (96 and 50 months respectively) and were observed to have a higher proportion of patients reporting CSU duration of 10 years or longer (33% and 25%, p = 0.033 and p = 0.036 respectively). Patients with co-existing autoimmune/thyroid disease (19%) trended towards a shorter median duration of CSU (37 months). 54 patients (75%) reported sleep disturbance and 29 patients (43%) required emergency room visit(s) for symptomatic control. 84% of patients who trialed second generation antihistamines reported a response to treatment, while 73% of patients who trialed omalizumab reported a response to treatment. Patients using alternative medicine such as acupuncture, traditional Chinese medicine and naturopathic medicine had lower reported response rates (20–29%) to treatment.

Conclusions

The natural history of CSU may be longer than previously reported with our study finding a median duration of symptoms of nearly 4 years with one-third of patients reporting a relapsing/remitting disease course. Younger age of onset, a relapsing/remitting disease course and angioedema may predict a longer duration of CSU, whereas older age of onset and co-existing autoimmune/thyroid disease may predict a shorter duration of CSU. Reported symptomatic benefit was higher from guidelines based pharmacologic therapy versus various alternative medicines.
Schools overcoming the digital divide: in depth analyses towards organizational resilience in the computer and information literacy domain
Authors: Drossel Kerstin , Eickelmann Birgit , Vennemann Mario
Published: July 2020

Background

The ongoing digitalization poses new challenges for schools concerning students’ digital skills. In this context, the International Computer and Information Literacy Study (IEA-ICILS 2018) has identified substantial social disparities concerning computer and information literacy of grade 8 students. Furthermore, it has been observed that many schools, especially those located in socioeconomically challenged areas, are particularly engaged in supporting students’ digital literacy and innovatively designing learning processes with information and communications technology (ICT). Empirical studies have made it apparent that some schools have high average achievements concerning domains such as reading literacy and mathematics in spite of socioeconomically challenged student bodies. These schools are regarded as being organizationally resilient. This contribution focusses on these organizationally resilient schools with regard to the domain of computer and information literacy. It aims to investigate how these schools can be classified as a typology according to selected school and/or teacher characteristics.

Methods

As a first step, representative samples of IEA-ICILS 2018 are used to identify organizationally resilient schools by using students’ achievement measures (plausible values) and their background information regarding their families’ socio-economic status. In order to develop a typology, latent profile analyses (LPA) are conducted by using input and process indicators on the school level, which have been proven to be relevant for implementation through existing empirical research.

Results

About one twentieth of the schools examined in this contribution can be regarded as organizationally resilient and can be allocated onto a typology of three school types that are characterized by different school-level factors.

Conclusions

The international comparison permits the conclusion that the phenomenon of organizational resilience is also existent with regard to the content domain of computer and information literacy. However, the proportion of resilient schools is subject to considerable variation between countries.
Correction to: Cardiac death after extreme physical and mental trauma—case report
Authors: Nedić Dalibor , Pilija Vladimir
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Correction to: Excited delirium syndrome from psychostimulant abuse can mimic a violent scene of death
Authors: Jothee Shatishraj , Shafie Mohamed Swarhib , Nor Faridah Mohd
Published: July 2020

An amendment to this paper has been published and can be accessed via the original article.
Isolation, molecular characterization of indigenous Beauveria bassiana isolate, using ITS-5.8 s rDNA region and its efficacy against the greatest wax moth, Galleria mellonella L. (Lepidoptera: Pyralidae) as a model insect
Authors: Fergani Yasmin A. , Yehia Ramy S.
Published: July 2020

The entomopathogenic fungi (EPF), as a biological control agent, can provide an alternative option for high-risk insecticides. Beauveria bassiana is one of the most potential EPF of pest control all over the world. The EPF isolate Y-F_ITS1 was isolated from Egyptian fauna on Beauveria-specific selective medium (BS medium). Molecular screening of the B. bassiana isolate, using PCR amplification with B. bassiana-specific primers and nucleotide sequence analysis of the internal transcribed spacer (ITS) region, confirmed the isolate as B. bassiana (accession no. [MK773644.1]). Efficacy of the isolate Y-F_ITS1 was examined against fourth instar larvae of Galleria mellonella L. as a model insect using concentrations from 104 to 107 spores ml−1 in a contact toxicity assay under laboratory conditions. The pathogenicity experiment showed that all the tested concentrations caused mortalities ranged from 75 to 98.33%, within 5 days posttreatment with cumulative mortalities, reached 100%, before 7 days with typical symptoms of infection and sporulation. Further investigations are needed to prove its efficacy against different economic pests as a credible candidate of integrated pest management (IPM) program.
Diagnosis of peripheral neuropathy
Authors: Lehmann Helmar C. , Wunderlich Gilbert , Fink Gereon R. , Sommer Claudia
Published: July 2020

Introduction

Peripheral neuropathy represents a spectrum of diseases with different etiologies. The most common causes are diabetes, exposure to toxic substances including alcohol and chemotherapeutics, immune-mediated conditions, and gene mutations. A thorough workup including clinical history and examination, nerve conduction studies, and comprehensive laboratory tests is warranted to identify treatable causes.

First steps

The variability of symptoms allows distinguishing characteristic clinical phenotypes of peripheral neuropathy that should be recognized in order to stratify the diagnostic workup accordingly. Nerve conduction studies are essential to determine the phenotype (axonal versus demyelinating) and severity. Laboratory tests, including genetic testing, CSF examination, nerve imaging, and nerve biopsy, represent additional clinical tests that can be useful in specific clinical scenarios.

Comments

We propose a flow chart based on five common basic clinical patterns of peripheral neuropathy. Based on these five clinical phenotypes, we suggest differential diagnostic pathways in order to establish the underlying cause.

Conclusions

The recognition of characteristic clinical phenotypes combined with nerve conduction studies allows pursuing subsequent diagnostic pathways that incorporate nerve conduction studies and additional diagnostic tests. This two-tiered approach promises higher yield and better cost-effectiveness in the diagnostic workup in patients with peripheral neuropathy.
Electrophysiological study of posterior antebrachial cutaneous nerve in a sample of normal subjects
Authors: Saba Emmanuel Kamal Aziz
Published: July 2020

Backgrounds

Posterior antebrachial cutaneous nerve sensory conduction study is clinically essential for the assessment of its integrity and for the localization of radial nerve lesions. The aim of the study was to assess posterior antebrachial cutaneous nerve sensory antidromic conduction technique and to obtain normal reference values for different sensory nerve action potential parameters of this nerve among a sample of Egyptian population.

Results

The current study included 120 upper limbs of 60 apparently healthy subjects [35 (58.3%) women]. Their mean age was 39.20 ± 11.95 years. The posterior antebrachial cutaneous nerve was recorded in all upper limbs (100%). The values (mean ± standard deviation) for the posterior antebrachial cutaneous nerve sensory nerve action potential onset latency were 2.05 ± 0.25 ms, peak latency was 2.63 ± 0.28 ms, conduction velocity was 60.50 ± 5.38 m/s, amplitude was 11.04 ± 4.26 μV, and inter-side sensory nerve action potential amplitude ratio was 0.69 ± 0.17. There were no statistically significant differences between men and women, as well as between right and left upper limbs regarding different posterior antebrachial cutaneous sensory nerve action potential parameters. There were no statistically significant correlations between participants’ age and anthropometric measures (i.e., height, weight, and body mass index) with different posterior antebrachial cutaneous nerve sensory nerve action potential parameters. There were no statistically significant adjusted effects of age, gender, and anthropometric measures on different posterior antebrachial cutaneous nerve sensory nerve action potential parameters in multiple linear regression analysis by controlling all other physiologic factors.

Conclusions

This research provides an applicable electrophysiological technique and normal reference values for the posterior antebrachial cutaneous nerve sensory conduction study.
Flying solo in Myanmar: case study on challenges and important lessons learned by an early career psychiatrist in a district setting
Authors: Yadanar Su Myat , Htoo Nay Chi , Zaw Thant , Pang Nicholas Tze Ping , Chua Sze Hung , Loo Jiann Lin
Published: July 2020

The transition from trainee early career psychiatrist (ECP) to independent practitioner can be challenging. Upon completion of training in well-equipped academic settings, an ECP from Myanmar is required to serve in a divisional hospital for at least 3 years. Significant challenges are faced by ECPs practising solo in divisional hospitals, including inexperience in administrative aspects, lack of future-proof training, scarcity of resources and facilities, struggles in the provision of holistic biopsychosocial treatment, work–life imbalance, and limited career advancement and access to continuous training. The solutions tried thus far include the incorporation of information and communication technology in training, gathering support and distant supervision from both local and international settings, and task shifting. Bigger challenges are often rewarded by faster growth, and difficult times stimulate creative solutions. The sacrifice of these solo ECPs has significantly improved the mental health service of Myanmar district regions.
Hypoglycemia and Islet Dysfunction Following Oral Glucose Tolerance Testing in Pancreatic-Insufficient Cystic Fibrosis
Authors: Kilberg Marissa J , Harris Clea , Sheikh Saba , Stefanovski Darko , Cuchel Marina , Kubrak Christina , Hadjiliadis Denis , Rubenstein Ronald C , Rickels Michael R , Kelly Andrea
Published: July 2020

Context

Oral glucose tolerance test (OGTT)-related hypoglycemia is common in pancreatic-insufficient cystic fibrosis (PI-CF), but its mechanistic underpinnings are yet to be established.

Objective

To delineate the mechanism(s) underlying OGTT-related hypoglycemia.

Design and Setting

We performed 180-minute OGTTs with frequent blood sampling in adolescents and young adults with PI-CF and compared results with those from a historical healthy control group. Hypoglycemia (Hypo[+]) was defined as plasma glucose <65 mg/dL. We hypothesized that CF-Hypo[+] would demonstrate impaired early phase insulin secretion and persistent late insulin effect compared with control-Hypo[+], and explored the contextual counterregulatory response.

Main Outcome Measure

OGTT 1-hour and nadir glucose, insulin, C-peptide, and insulin secretory rate (ISR) incremental areas under the curve (AUC) between 0 and 30 minutes (early) and between 120 and 180 minutes (late), and Δglucagon120-180min and Δfree fatty acids (FFAs)120-180min were compared between individuals with CF and control participants with Hypo[+].

Results

Hypoglycemia occurred in 15/23 (65%) patients with CF (43% female, aged 24.8 [14.6-30.6] years) and 8/15 (55%) control participants (33% female, aged 26 [21-38] years). The CF-Hypo[+] group versus the control-Hypo[+] group had higher 1-hour glucose (197 ± 49 vs 139 ± 53 mg/dL; P = 0.05) and lower nadir glucose levels (48 ± 7 vs 59 ± 4 mg/dL; P < 0.01), while insulin, C-peptide, and ISR-AUC0-30 min results were lower and insulin and C-peptide, and AUC120-180min results were higher (P < 0.05). Individuals with CF-Hypo[+] had lower Δglucagon120-180min and ΔFFA120-180min compared with the control-Hypo[+] group (P < 0.01).

Conclusions

OGTT-related hypoglycemia in PI-CF is associated with elevated 1-hour glucose, impaired early phase insulin secretion, higher late insulin exposure, and less increase in glucagon and FFAs. These data suggest that hypoglycemia in CF is a manifestation of islet dysfunction including an impaired counterregulatory response.
Immune Checkpoint Inhibitor-induced Thyroid Dysfunction Is Associated with Higher Body Mass Index
Authors: Pollack Rena , Ashash Amit , Cahn Avivit , Rottenberg Yakir , Stern Hagay , Dresner-Pollak Rivka
Published: July 2020

Context

Obesity is a proinflammatory metabolic state that may play a role in the development of immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy.

Objective

To characterize the association between body mass index (BMI) and thyroid irAEs.

Methods

We performed a single-center, retrospective analysis of 185 cancer patients treated with anti-PD-1/L1 from January 2014 to December 2018. Patients with normal thyroid function at baseline and available BMI were included.

Main outcome measures

The primary endpoint was difference in BMI in patients who developed overt thyroid dysfunction versus those who remained euthyroid following anti-PD-1/L1 initiation. Additional endpoints included any (overt or subclinical) thyroid dysfunction, overt thyrotoxicosis or overt hypothyroidism, and time to development of dysfunction according to BMI.

Results

Any thyroid dysfunction developed in 72 (38.9%) patients and 41 (22.1%) developed overt thyroid dysfunction. Mean BMI was higher in those with overt thyroid dysfunction versus euthyroid (27.3 ± 6.0 vs 24.9 ± 4.5, P = .03). Development of overt thyrotoxicosis versus remaining euthyroid was associated with higher BMI (28.9 ± 5.9 vs 24.9 ± 4.5; P < .01), whereas overt hypothyroidism was not (26.7 ± 5.5 vs 24.9 ± 4.5, P = .10). Overt thyrotoxicosis developed within 57.5 (interquartile range [IQR] 31.8-78.8) days of treatment in the low-normal BMI group, 38.0 (IQR 26.8-40.5) days in the overweight group, and 23.0 (IQR 21.0-28.0) days in the obese group (P = .02).

Conclusions

Patients treated with PD-1/L1 inhibitors were more likely to develop thyroid irAEs, specifically overt thyrotoxicosis, with increasing BMI. Overt thyrotoxicosis occurred earlier in obese versus leaner patients. These data highlight the complex interplay between obesity and immune response in immune checkpoint inhibitor-treated patients.
Standardizing Monte Carlo simulation parameters for a reproducible dose-averaged linear energy transfer
Authors: Koh Wei Yang Calvin , Tan Hong Qi , Ang Khong Wei , Park Sung Yong , Lew Wen Siang , Lee James Cheow Lei
Published: July 2020

Objective:

Dose-averaged linear energy transfer (LETD) is one of the factors which determines relative biological effectiveness (RBE) for treatment planning in proton therapy. It is usually determined from Monte Carlo (MC) simulation. However, no standard simulation protocols were established for sampling of LETD. Simulation parameters like maximum step length and range cut will affect secondary electrons production and have an impact on the accuracy of dose distribution and LETD. We aim to show how different combinations of step length and range cut in GEANT4 will affect the result in sampling of LETD using different MC scoring methods.

Methods:

In this work, different step length and range cut value in a clinically relevant voxel geometry were used for comparison. Different LETD scoring methods were established and the concept of covariance between energy deposition per step and step length is used to explain the differences between them.

Results:

We recommend a maximum step length of 0.05 mm and a range cut of 0.01 mm in MC simulation as this yields the most consistent LETD value across different scoring methods. Different LETD scoring methods are also compared and variation up to 200% can be observed at the plateau of 80 MeV proton beam. Scoring Method one has one of the lowest percentage differences compared across all simulation parameters.

Conclusion:

We have determined a set of maximum step length and range cut parameters to be used for LETD scoring in a 1 mm voxelized geometry. LETD scoring method should also be clearly defined and standardized to facilitate cross-institutional studies.

Advances in knowledge:

Establishing a standard simulation protocol for sampling LETD would reduce the discrepancy when comparing data across different centres, and this can improve the calculation for RBE.
Pamięć konstruowana
Authors: Danek Magdalena
Published: July 2020

Built Memory. ‘Cursed Soldiers’ in the Narratives of Polish Opinion-Forming Weeklies

The activity of the anti-communist underground was for many years a marginalised element both in historical education and public discourse. However, we have noticed a significant turn in this matter recently. This process is manifested by specific ‘acts of remembrance,’ such as honorary funerals of the exhumed cursed soldiers’ bodies. What is crucial is that in the background we can observe an extremely important action of constructing memory about the activists of the Polish underground, in which several separate narratives can be distinguished. Mass media play a key role in this process. They create interpretative schemes using among others the ‘post-memory’ testimonies and influence on constructing social memory and post-memory itself. The aim of this article is to recreate interpretative schemes concerning the life and activity of the cursed soldiers in the following Polish weeklies: Gość Niedzielny, Polityka, Newsweek Polska and wSieci. My selection was determined by their current sales results. The method used in the study is framing analysis.