bluuebunny/crossref_metadata_2025 huggingface dataset:
Patients’, pharmacists’, and prescribers’ attitude toward using blockchain and machine learning in a proposed ePrescription system: online survey
Authors: Aldughayfiq Bader , Sampalli Srinivas
Published: January 2022

Objective

To evaluate the attitudes of the parties involved in the system toward the new features and measure the potential benefits of introducing the use of blockchain and machine learning (ML) to strengthen the in-place methods for safely prescribing medication. The proposed blockchain will strengthen the security and privacy of the patient’s prescription information shared in the network. Once the ePrescription is submitted, it is only available in read-only mode. This will ensure there is no alteration to the ePrescription information after submission. In addition, the blockchain will provide an improved tracking mechanism to ensure the originality of the ePrescription and that a prescriber can only submit an ePrescription with the patient’s authorization. Lastly, before submitting an ePrescription, an ML algorithm will be used to detect any anomalies (eg, missing fields, misplaced information, or wrong dosage) in the ePrescription to ensure the safety of the prescribed medication for the patient.

Methods

The survey contains questions about the features introduced in the proposed ePrescription system to evaluate the security, privacy, reliability, and availability of the ePrescription information in the system. The study population is comprised of 284 respondents in the patient group, 39 respondents in the pharmacist group, and 27 respondents in the prescriber group, all of whom met the inclusion criteria. The response rate was 80% (226/284) in the patient group, 87% (34/39) in the pharmacist group, and 96% (26/27) in the prescriber group.

Key Findings

The vast majority of the respondents in all groups had a positive attitude toward the proposed ePrescription system’s security and privacy using blockchain technology, with 72% (163/226) in the patient group, 70.5% (24/34) in the pharmacist group, and 73% (19/26) in the prescriber group. Moreover, the majority of the respondents in the pharmacist (70%, 24/34) and prescriber (85%, 22/26) groups had a positive attitude toward using ML algorithms to generate alerts regarding prescribed medication to enhance the safety of medication prescribing and prevent medication errors.

Conclusion

Our survey showed that a vast majority of respondents in all groups had positive attitudes toward using blockchain and ML algorithms to safely prescribe medications. However, a need for minor improvements regarding the proposed features was identified, and a post-implementation user study is needed to evaluate the proposed ePrescription system in depth.
Evaluation of convection flow and entropy generation in a wavy cubical container with nanofluid and embedded cylinder
Authors: Alsabery Ammar I , Yazdi Mohammad H , Solomin Evgeny , Öztop Hakan F , Hashim Ishak
Published: January 2022

This work examines steady convection heat transfer and entropy generation in a wavy cubical container with Al2O3–water nanofluid and the solid cylinder. An isothermal embedded heater of finite width is located within the left vertical surface center of the container. All surfaces are insulated, except that the right wavy surface is kept cold, and the left wall is partially heated. The Boussinesq approximation is assumed, and three-dimensional simulations of governing equations have been applied to utilize the Galerkin weighted residual finite-element approach. Numerical results for the three-dimensional patterns of nanofluid flow, iso-temperature surfaces, and isentropic lines are given. The local Nusselt number adjacent to the left and interface surfaces within the container and solid cylinder and Bejan number have been examined for different values of the Rayleigh number, nanoparticle volume fraction, number of undulations and heater length, and cylinder radius. The results indicate that the optimal local heat transfer between the solid cylinder and container declines with the increased cylinder radius, which yields an imperfect nanofluid flow circulation.
Shredded
Authors: Ramírez-Gutiérrez Camilo , Quiroga-Villamarín Daniel R
Published: January 2022

From 2012 to 2016, the Colombian Government and the FARC-EP guerilla group sought to end the region’s longest non-international armed conflict. Under the auspices of the international community, this process drew from a complex series of practices and knowledge often known as ‘transitional justice’. Indeed, international expertise — in law and other fields — was also actively mobilized by both parties, as well as civil society and the anti-peace opposition, to contest the meaning of these terms. On paper, the peace agreement adopted a cutting-edge and comprehensive system aimed at delivering truth, justice, reparation, and non-repetition (the SIVJRNR), including both judicial and extrajudicial mechanisms following international standards and best practices. Yet in practice, the situation became increasingly dire after the peace agreement was narrowly voted down in October 2016. Two years later, having entered government, the former populist opposition proudly announced its plan to shred the peace accord and the SIVJRNR (including its crown jewel: the Special Jurisdiction for Peace or JEP). In this context, this article seeks to identify and understand the strategies which might be adopted by transitional justice institutions to prevail against waves of populist misinformation and backlash. The Colombian experiment can offer important insights on how humanitarian actors can generate public narratives of reconciliation in our current dire times of mistrust.
Family Matters: Older Refugee Minors in Vienna and Factors for Resiliency
Authors: Seaman Mackenzie , Stites Elizabeth
Published: January 2022

European migration discourses emphasize that unaccompanied refugee minors (URMs) are one of Europe’s most vulnerable migrant groups. The absence of an adult caregiver often serves as the sole explanation for the heightened vulnerability of URMs vis-à-vis their accompanied counterparts. This article challenges the assumption that the absence of adult caregivers always breeds greater vulnerability among young refugees who have received international protection. Based on 72 surveys and 31 in-depth interviews with refugees who received international protection and who arrived in Vienna, Austria between the ages of 14 and 18, this article contributes to empirical analysis on the complex impact adult relative caregivers specifically have on the integration and resiliency of refugee youth. It explores the influence that family status has on employment, education, social connections and personal outlook and sense of belonging. We hypothesize that refugees who arrived as older URMs experience a financial and social autonomy, as well as benefit from a more advantageous legal and social treatment, speeding up their adaptation process and engendering greater resiliency. While the findings highlight that family matters, they also show that family may not play a ubiquitously positive role in young refugees’ adaptation process as previously assumed.
Influence of Soldiers’ Cardiorespiratory Fitness on Physiological Responses and Dropouts During a Loaded Long-distance March
Authors: Oeschger Regina , Roos Lilian , Wyss Thomas , Buller Mark J , Veenstra Bertil J , Gilgen-Ammann Rahel
Published: January 2022

Introduction

In military service, marching is an important, common, and physically demanding task. Minimizing dropouts, maintaining operational readiness during the march, and achieving a fast recovery are desirable because the soldiers have to be ready for duty, sometimes shortly after an exhausting task. The present field study investigated the influence of the soldiers’ cardiorespiratory fitness on physiological responses during a long-lasting and challenging 34 km march.

Materials and Methods

Heart rate (HR), body core temperature (BCT), total energy expenditure (TEE), energy intake, motivation, and pain sensation were investigated in 44 soldiers (20.3 ± 1.3 years, 178.5 ± 7.0 cm, 74.8 ± 9.8 kg, body mass index: 23.4 ± 2.7 kg × m−2, peak oxygen uptake ($\dot{\rm{V}}$O2peak): 54.2 ± 7.9 mL × kg−1 × min−1) during almost 8 hours of marching. All soldiers were equipped with a portable electrocardiogram to record HR and an accelerometer on the hip, all swallowed a telemetry pill to record BCT, and all filled out a pre- and post-march questionnaire. The influence of aerobic capacity on the physiological responses during the march was examined by dividing the soldiers into three fitness groups according to their $\dot{\rm{V}}$O2peak.

Results

The group with the lowest aerobic capacity ($\dot{\rm{V}}$O2peak: 44.9 ± 4.8 mL × kg−1 × min−1) compared to the group with the highest aerobic capacity ($\dot{\rm{V}}$O2peak: 61.7 ± 2.2 mL × kg−1 × min−1) showed a significantly higher (P < .05) mean HR (133 ± 9 bpm and 125 ± 8 bpm, respectively) as well as peak BCT (38.6 ± 0.3 and 38.4 ± 0.2 °C, respectively) during the march. In terms of recovery ability during the break, no significant differences could be identified between the three groups in either HR or BCT. The energy deficit during the march was remarkably high, as the soldiers could only replace 22%, 26%, and 36% of the total energy expenditure in the lower, middle, and higher fitness group, respectively. The cardiorespiratory fittest soldiers showed a significantly higher motivation to perform when compared to the least cardiorespiratory fit soldiers (P = .002; scale from 1 [not at all] to 10 [extremely]; scale difference of 2.3). A total of nine soldiers (16%) had to end marching early: four soldiers (21%) in the group with the lowest aerobic capacity, five (28%) in the middle group, and none in the highest group.

Conclusion

Soldiers with a high $\dot{\rm{V}}$O2peak showed a lower mean HR and peak BCT throughout the long-distance march, as well as higher performance motivation, no dropouts, and lower energy deficit. All soldiers showed an enormous energy deficit; therefore, corresponding nutritional strategies are recommended.
Purifying Selection Determines the Short-Term Time Dependency of Evolutionary Rates in SARS-CoV-2 and pH1N1 Influenza
Authors: Ghafari Mahan , du Plessis Louis , Raghwani Jayna , Bhatt Samir , Xu Bo , Pybus Oliver G , Katzourakis Aris
Published: January 2022

High-throughput sequencing enables rapid genome sequencing during infectious disease outbreaks and provides an opportunity to quantify the evolutionary dynamics of pathogens in near real-time. One difficulty of undertaking evolutionary analyses over short timescales is the dependency of the inferred evolutionary parameters on the timespan of observation. Crucially, there are an increasing number of molecular clock analyses using external evolutionary rate priors to infer evolutionary parameters. However, it is not clear which rate prior is appropriate for a given time window of observation due to the time-dependent nature of evolutionary rate estimates. Here, we characterize the molecular evolutionary dynamics of SARS-CoV-2 and 2009 pandemic H1N1 (pH1N1) influenza during the first 12 months of their respective pandemics. We use Bayesian phylogenetic methods to estimate the dates of emergence, evolutionary rates, and growth rates of SARS-CoV-2 and pH1N1 over time and investigate how varying sampling window and data set sizes affect the accuracy of parameter estimation. We further use a generalized McDonald–Kreitman test to estimate the number of segregating nonneutral sites over time. We find that the inferred evolutionary parameters for both pandemics are time dependent, and that the inferred rates of SARS-CoV-2 and pH1N1 decline by ∼50% and ∼100%, respectively, over the course of 1 year. After at least 4 months since the start of sequence sampling, inferred growth rates and emergence dates remain relatively stable and can be inferred reliably using a logistic growth coalescent model. We show that the time dependency of the mean substitution rate is due to elevated substitution rates at terminal branches which are 2–4 times higher than those of internal branches for both viruses. The elevated rate at terminal branches is strongly correlated with an increasing number of segregating nonneutral sites, demonstrating the role of purifying selection in generating the time dependency of evolutionary parameters during pandemics.
Experimental demonstration of operon formation catalyzed by insertion sequence
Authors: Kanai Yuki , Tsuru Saburo , Furusawa Chikara
Published: January 2022

Operons are a hallmark of the genomic and regulatory architecture of prokaryotes. However, the mechanism by which two genes placed far apart gradually come close and form operons remains to be elucidated. Here, we propose a new model of the origin of operons: Mobile genetic elements called insertion sequences can facilitate the formation of operons by consecutive insertion–deletion–excision reactions. This mechanism barely leaves traces of insertion sequences and thus difficult to detect in nature. In this study, as a proof-of-concept, we reproducibly demonstrated operon formation in the laboratory. The insertion sequence IS3 and the insertion sequence excision enhancer are genes found in a broad range of bacterial species. We introduced these genes into insertion sequence-less Escherichia coli and found that, supporting our hypothesis, the activity of the two genes altered the expression of genes surrounding IS3, closed a 2.7 kb gap between a pair of genes, and formed new operons. This study shows how insertion sequences can facilitate the rapid formation of operons through locally increasing the structural mutation rates and highlights how coevolution with mobile elements may shape the organization of prokaryotic genomes and gene regulation.
Gain of C-Ala enables AlaRS to target the L-shaped tRNAAla
Authors: Antika Titi Rindi , Chrestella Dea Jolie , Ivanesthi Indira Rizqita , Rida Gita Riswana Nawung , Chen Kuan-Yu , Liu Fu-Guo , Lee Yi-Chung , Chen Yu-Wei , Tseng Yi-Kuan , Wang Chien-Chia
Published: January 2022

Unlike many other aminoacyl-tRNA synthetases, alanyl-tRNA synthetase (AlaRS) retains a conserved prototype structure throughout biology. While Caenorhabditis elegans cytoplasmic AlaRS (CeAlaRSc) retains the prototype structure, its mitochondrial counterpart (CeAlaRSm) contains only a residual C-terminal domain (C-Ala). We demonstrated herein that the C-Ala domain from CeAlaRSc robustly binds both tRNA and DNA. It bound different tRNAs but preferred tRNAAla. Deletion of this domain from CeAlaRSc sharply reduced its aminoacylation activity, while fusion of this domain to CeAlaRSm selectively and distinctly enhanced its aminoacylation activity toward the elbow-containing (or L-shaped) tRNAAla. Phylogenetic analysis showed that CeAlaRSm once possessed the C-Ala domain but later lost most of it during evolution, perhaps in response to the deletion of the T-arm (part of the elbow) from its cognate tRNA. This study underscores the evolutionary gain of C-Ala for docking AlaRS to the L-shaped tRNAAla.
A new twist on graphene: an interview with Pablo Jarillo-Herrero and Allan MacDonald
Authors: Ball Philip
Published: January 2022

Graphene is the building block of graphite, made of carbon atoms bonded into sheets of hexagonal rings just a single atom thick. Although such isolated sheets had been predicted for many decades to exist, and had been grown on other surfaces, interest in this material exploded after the discovery in 2004 that single sheets could be made easily and cheaply by separating them mechanically from graphite flakes (a process called exfoliation). Although graphene is often advertised as a ‘wonder material’—electronically conducting, transparent and extremely strong and flexible—much of the interest in it is more fundamental. As a 2D conductor, graphene shows unusual electronic and magnetic properties that enable the study of quantum-mechanical effects of confinement and of correlations between electron motions—some of which might find applications in electronic devices. The excitement of this discovery was reflected in the award of the 2010 Nobel Prize in Physics to two pioneers in the field: Andre Geim and Konstantin Novoselov of the University of Manchester in the UK.

This rich behavior is broadened still further when two graphene sheets are brought close enough to interact with one another. In particular, the electronic properties may then depend on the relative orientation of the sheets: how aligned the two ‘honeycomb’ lattices are. Two grids superimposed on one another may create ‘superlattices’: regularities at larger scales than the grid spacing, due to registry (commensurability) between the two at certain angles. This so-called moiré effect is sometimes evident for two closely spaced grid-like fences seen from afar. Experimentally exploring the electronic properties of such ‘twisted bilayer graphene’ requires an ability to precisely control the position and orientation of the two sheets. These phenomena are now recognized as generic to other 2D materials, such as hexagonal sheets of boron nitride. They have revealed a fertile playground for condensed-matter physics. In particular, striking electronic properties appear at certain ‘magic-angle’ twists of the layers.

NSR spoke to two of the leading experts in the study of magic-angle twisted bilayer graphene (MATBG): experimentalist Pablo Jarillo-Herrero of the Massachusetts Institute of Technology and theorist Allan MacDonald of the University of Texas at Austin.
An Evaluation of Evidence Underpinning Management Recommendations in Tobacco Use Disorder Clinical Practice Guidelines
Authors: Streck Sam , McIntire Ryan , Canale Lawrence , Michael Anderson J , Hartwell Micah , Torgerson Trevor , Dunn Kelly , Vassar Matt
Published: January 2022

Introduction

Clinical practice guidelines(CPGs) are important tools for medical decision-making. Given the high prevalence and financial burden associated with tobacco use disorder(TUD), it is critical that recommendations within CPGs are based on robust evidence. Systematic reviews(SRs) are considered the highest level of evidence, thus, we evaluated the quality of SRs underpinning CPG recommendations for TUD.

Methods

We used PubMed to search for CPGs relating to TUD published between January 1, 2010 and May 21, 2021. SRs were extracted from CPG references and evaluated using Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA) and A MeaSurement Tool to Assess Systematic Reviews(AMSTAR-2) tools. We then compared SRs conducted by the Cochrane Collaboration with non-Cochrane SRs using a Mann-Whitney U test and determined associations between PRISMA and AMSTAR-2 extracted characteristics using multiple regression.

Results

Our search generated 10 CPGs with 98 SRs extracted. Mean PRISMA completion was 74.7%(SD = 16.7) and mean AMSTAR-2 completion was 53.8%(SD = 22.0) across all guidelines. Cochrane SRs were more complete than non-Cochrane studies in the PRISMA and AMSTAR-2 assessments. The regression model showed a statistically significant association between PRISMA completion and AMSTAR-2 rating, with those classified as “low” or “moderate” quality having higher PRISMA completion than those with “critically low” ratings.

Conclusion

We found substandard adherence to PRISMA and AMSTAR-2 checklists across SRs cited in TUD CPGs. A lack of recent SRs in CPGs could lead to outdated recommendations. Therefore, frequent guideline updates with recently published evidence may ensure more accurate clinical recommendations and improve patient care.

Implications

Systematic reviews used to underpin clinical practice guideline recommendations influence treatment decisions and, ultimately, patient outcomes. We found that many systematic reviews underpinning tobacco use disorder guideline recommendations were out of date and unsatisfactory in reporting and quality. Thus, including newer systematic reviews containing more recently conducted trials and better reporting could alter recommendations and improve the rate of successful tobacco cessation attempts.
Impact of Covid-19 on Caller Characteristics and Quit Rates: Experience of Regional Tobacco Quitline From India
Authors: Pradeepkumar P C , Murthy Pratima , Lohit R P , Hegde Sudarshan , Chand Prabhat , Sethuraman Lakshmanan
Published: January 2022

Background

The tobacco epidemic is a major health concern amplified by Covid-19. We aimed to study differences in caller profiles to the regional tobacco quitline services of South India during the Covid-19 pandemic in comparison with the prepandemic.

Method

Using a descriptive cross-sectional research design, we examined registered caller profiles to the quitline between March and July 2019 (Prepandemic N = 7845) and the same months in 2020 (Covid-19 pandemic phase N = 6447) phases.

Results

The proportion of registered callers with an expressed intent to quit tobacco increased by 1.73 times during pandemic (16.7% versus 9.6%). Health concerns were cited as the major reason (93.25%) to quit tobacco in 2020 as compared to 2019 (88.02%). Cough (28.50%) and psychological difficulties (14.20%) were reported significantly more by RCs in 2020. Self-reported quit rates were significantly higher among RCs in 2020 as compared to 2019 on the quit day (2019—47.37% & 2020—77.54%, p = .001), at one week (2019—25.17% and 2020—56.06%, p = .001) as was one-month continuous abstinence (2019—11.88% and 2020—39.60%, p = .001).

Conclusion

The pandemic resulted in a greater intent to quit among registered callers to the quitline. However, awareness about the quitline services as well as other tobacco cessation services needs to be expanded to reach more tobacco users.

Implications

Pandemics offer an opportunity to change health risk behaviors. During the Covid-19 pandemic, callers to the tobacco quitline were more motivated to quit tobacco and attributed it to concerns about the health risks from tobacco use, particularly during the pandemic. Quit rates also increased significantly during the pandemic as compared to before. These gains in encouraging tobacco cessation need to be maintained beyond the pandemic by strengthening existing quitlines and other supports for tobacco cessation.
What’s Constitutional about Revolutions?
Authors: Arban Erika , Samararatne Dinesha
Published: January 2022

Theorists have flirted with the idea of revolution for quite some time, mainly exploring the political, social and constitutional implications of this idea. Revolutions are easily associated with images of violent upsurges, social unrest and overturning of ruling leaders. However, there is a close link between revolutions and constitutionalism more generally: in fact, a revolution is often followed by a new constitutional moment, and the idea of ‘revolution’ has even been used in the context of judicial decision making. In theoretical terms, the intersection between constitutions, constitutionalism and revolution has emerged as a theme in academic legal scholarship in the past few years.1 In this review article, we engage with one of the latest publications in this area, Constitutional Revolution by Jacobsohn and Roznai whose purpose is to offer a theoretical and comparative account of the concept of revolution as applied in/to constitutional law.

The article is structured as follows. First, we consider the central claim made in the book, and then comment on some of the methodological choices made by the authors. Next, we situate the book within the broader scholarship on revolutions, exploring the resurgence of the idea of (constitutional) revolutions as unfolded in the social sciences. We then try to ‘recast’ the concept of revolution in constitutional theory by exploring the analytical value of the theorisation and some limits to its application, reflecting on some of the tensions that emerge from such conceptualisation. Finally, we test the theory through the constitutional experiences of two jurisdictions not considered in the book: Sri Lanka and Italy.
Evaluation of Tumor DNA Sequencing Results in Patients with Gastric and Gastroesophageal Junction Adenocarcinoma Stratified by TP53 Mutation Status
Authors: Wood Anthony C , Zhang Yonghong , Mo Qianxing , Cen Ling , Fontaine Jacques , Hoffe Sarah E , Frakes Jessica , Dineen Sean P , Pimiento Jose M , Walko Christine M , Mehta Rutika
Published: January 2022

Background

Gastric cancer (GC) and gastroesophageal junction adenocarcinomas (GEJ) are molecularly diverse. TP53 is the most frequently altered gene with approximately 50% of patients harboring mutations. This qualitative study describes the distinct genomic alterations in GCs and GEJs stratified by TP53 mutation status.

Patients and Methods

Tumor DNA sequencing results of 324 genes from 3741 patients with GC and GEJ were obtained from Foundation Medicine. Association between gene mutation frequency and TP53 mutation status was examined using Fisher’s exact test. Functional gene groupings representing molecular pathways suggested to be differentially mutated in TP53 wild-type (TP53WT) and TP53 mutant (TP53MUT) tumors were identified. The association of the frequency of tumors containing a gene mutation in the molecular pathways of interest and TP53 mutation status was assessed using Fisher’s exact test with a P-value of <.01 deemed statistically significant for all analyses.

Results

TP53 mutations were noted in 61.6% of 2946 GCs and 81.4% of 795 GEJs (P < .001). Forty-nine genes had statistically different mutation frequencies in TP53WT vs. TP53MUT patients. TP53WT tumors more likely had mutations related to DNA mismatch repair, homologous recombination repair, DNA and histone methylation, Wnt/B-catenin, PI3K/Akt/mTOR, and chromatin remodeling complexes. TP53MUT tumors more likely had mutations related to fibroblast growth factor, epidermal growth factor receptor, other receptor tyrosine kinases, and cyclin and cyclin-dependent kinases.

Conclusion

The mutational profiles of GCs and GEJs varied according to TP53 mutation status. These mutational differences can be used when designing future studies assessing the predictive ability of TP53 mutation status when targeting differentially affected molecular pathways.
Efficacy of Infliximab Dose Escalation in Patients with Refractory Immunotherapy-Related Colitis: A Case Series
Authors: Harris Jessica P , Postow Michael A , Faleck David M
Published: January 2022

Immune checkpoint inhibitor-related colitis is a common complication of immunotherapy use in patients with cancer. Current guidelines recommend treatment with standard dose infliximab (IFX) for corticosteroid-refractory colitis; however, this case series suggests IFX dose escalation may be a viable treatment option for refractory cases.
Chlorophyll and Pheophytin Dephytylating Enzymes Required for Efficient Repair of PSII in Synechococcus elongatus PCC 7942
Authors: Takatani Nobuyuki , Uenosono Makoto , Hara Yuriko , Yamakawa Hisanori , Fujita Yuichi , Omata Tatsuo
Published: January 2022

The Chlorophyll Dephytylase1 (CLD1) and pheophytinase (PPH) proteins of Arabidopsis thaliana are homologous proteins characterized respectively as a dephytylase for chlorophylls (Chls) and pheophytin a (Phein a) and a Phein a-specific dephytylase. Three genes encoding CLD1/PPH homologs (dphA1, dphA2 and dphA3) were found in the genome of the cyanobacterium Synechococcus elongatus PCC 7942 and shown to be conserved in most cyanobacteria. His6-tagged DphA1, DphA2 and DphA3 proteins were expressed in Escherichia coli, purified to near homogeneity, and shown to exhibit significant levels of dephytylase activity for Chl a and Phein a. Each DphA protein showed similar dephytylase activities for Chl a and Phein a, but the three proteins were distinct in their kinetic properties, with DphA3 showing the highest and lowest Vmax and Km values, respectively, among the three. Transcription of dphA1 and dphA3 was enhanced under high-light conditions, whereas that of dphA2 was not affected by the light conditions. None of the dphA single mutants of S. elongatus showed profound growth defects under low (50 µmol photons m−2 s−1) or high (400 µmol photons m−2 s−1) light conditions. The triple dphA mutant did not show obvious growth defects under these conditions, either, but under illumination of 1,000 µmol photons m−2 s−1, the mutant showed more profound growth retardation compared with wild type (WT). The repair of photodamaged photosystem II (PSII) was much slower in the triple mutant than in WT. These results revealed that dephytylation of Chl a or Phein a or of both is required for efficient repair of photodamaged PSII.
Defining the minimal important change (MIC) and meaningful change value (MCV) for the Psoriatic Arthritis Disease Activity Score (PASDAS) in a routine practice cohort of patients with psoriatic arthritis
Authors: Mulder Michelle L M , Bertram Anouk M , Wenink Mark H , Vriezekolk Johanna E
Published: January 2022

Objective

The aim of the study was to determine the Minimal Important Change (MIC) values and Meaningful Change (MCV) values for the Psoriatic Arthritis Disease Activity Score (PASDAS) and the Standard Error of Measurement (s.e.m.) of the PASDAS.

Methods

The routine practice data for 544 patients with PsA was available for analysis. An anchor-based method using linear regression analyses was used to determine the MICs and MCVs for the PASDAS. With this anchor-based method, we compared changes in the PASDAS score with an external reference (anchor). The anchor question inquired whether the patient’s well-being had changed since their previous visit. It consisted of a 7-point Likert scale (range: very much improved to very much deteriorated). Interperiod correlation matrix analysis was performed to determine the s.e.m.

Results

The overall MIC and MCV for the PASDAS were 0.67 (95% CI: 0.55, 0.79) and 1.34 (95% CI: 1.21, 1.46), respectively. Results for improvement and deterioration were 0.65 (95% CI: 0.46, 0.83) and 0.71 (95% CI: 0.49, 0.93) for the MIC, respectively, and 1.29 (95% CI: 1.11, 1.48) and 1.42 (95% CI: 1.19, 1.64) for the MCV, respectively. The s.e.m. was determined at 0.81.

Conclusion

The MIC for the PASDAS is a tool for physicians treating patients with PsA enabling them to give context to the patient’s perspective of disease activity, while the MCV might aid the use of the PASDAS in PsA clinical trials.
The Womb in Labour: Representing the Woman’s Body as an Active Vessel in Hildegard of Bingen’s Cause et Cure
Authors: Lee Minji
Published: January 2022

Hildegard of Bingen was a German nun who wrote medical treatises in the Middle Ages that interpreted the female body as a positive and purifying agent of God’s creation and salvation at a time when negative connotations of female physicality prevailed in medicine. In particular, she described the female body as an active vessel, in opposition to the predominant image of the female body as passive. Her explanations of conception, pregnancy and childbirth in her medical book Cause et Cure represent the female body as actively advancing, nourishing, purifying and caring for future generations in the form of the baby, creating an analogy between the woman’s power of reproduction and God’s power of creation. This article concludes that Hildegard’s vessel imagery is a result of her high regard for the female body and its capacity for reproduction. Hildegard’s novel interpretation of the vessel provides a uniquely woman-empowering image for discussing the broader complex of gender and body in medieval medicine.
Unreported mixed Plasmodium species infection may increase vivax malaria in India: a challenge for malaria elimination
Authors: Nema Shrikant , Singh Akansha , Krishna Sri , Poriya Rajan , Dubey Shivangi , Ali Nazia A , Singh Mrigendra Pal , Verma Anil Kumar , Das Aparup , Bharti Praveen Kumar
Published: January 2022

Background

In India, there are several malaria-endemic regions where non-falciparum species coexist with Plasmodium falciparum. Traditionally, microscopy and rapid diagnostic tests are used for the diagnosis of malaria. Nevertheless, microscopy often misses the secondary malaria parasite in mixed-infection cases due to various constraints. Misdiagnosis/misinterpretation of Plasmodium species leads to improper treatment, as the treatment for P. falciparum and Plasmodium vivax species is different, as per the national vector-borne disease control program in India.

Methods

Blood samples were collected from malaria-endemic regions (Jharkhand, Madhya Pradesh, Chhattisgarh, Maharashtra, Odisha, Assam, Meghalaya, Mizoram and Telangana) of India covering almost the entire country. Molecular diagnosis of Plasmodium species was carried out among microscopically confirmed P. falciparum samples collected during a therapeutic efficacy study in different years.

Results

The polymerase chain reaction analysis revealed a high prevalence (18%) of mixed malaria parasite infections among microscopically confirmed P. falciparum samples from malaria patients that are either missed or left out by microscopy.

Conclusions

Deployment of molecular tools in areas of mixed species infection may prove vital for accurate diagnosis and treatment of malaria. Further, it will help in achieving the goal of malaria elimination in India.
Stricken Before Election: Presidential Health Crises From 1880 to 2020
Authors: Barr Justin , Pappas Theodore N.
Published: January 2022

Between 1880 and today, 6 presidents have suffered major health crises just before their reelection campaigns. Ranging from Chester Arthur’s development of Bright’s Disease to Donald Trump contracting COVID-19, diseases and their treatments varied considerably. More interesting than the medical management, however, is the political maneuvering around each and the extraordinary lengths Presidents went to demonstrate their health to the American people. This article reviews these episodes, comparing and contrasting how each administration handled their crisis and what effect it had on the ensuing election—and thus the history of the United States.
Recent advances in radiosensitivity determinants in melanoma
Authors: Krayem Mohammad , Ghanem Ghanem E. , Van Gestel Dirk
Published: January 2022

Purpose of review

Radiotherapy has been proven to be useful but insufficient in melanoma management due to the intrinsic radioresistance of melanoma cells. Elucidation of the molecular mechanisms and pathways related to resistance/sensitivity to radiotherapy in melanoma is of paramount importance. In this review, we will summarize and discuss the recent ‘discoveries’ and advances in radiosensitivity determinants in melanoma.

Recent findings

The different levels of radiosensitivity among the various melanoma tumors could be attributed to the DNA damage signaling and repair proteins, tumor microenvironment, hypoxia, cell metabolism, glutathione and redox balance, protein kinase signaling pathways as well as pigmentation and melanin content.

It is therapeutically important to elucidate the factors involved in radiation resistance/sensitivity of melanoma. More importantly, improving radiosensitivity may ‘widen the clinical utility’ in melanoma of this important therapeutic modality.
Association of sleep disturbance with Parkinson disease: evidence from the Women's Health Initiative
Authors: Beydoun Hind A. , Naughton Michelle J. , Beydoun May A. , Shadyab Aladdin H. , Brunner Robert L. , Chen Jiu-Chiuan , Espeland Mark , Shumaker Sally A. , Zonderman Alan B.
Published: January 2022

Objective:

To examine the association of sleep disturbance with Parkinson disease (PD) during 10+ years of follow-up among postmenopausal women, 50 to 79 years of age at baseline.

Methods:

Longitudinal data on 130,502 study-eligible women (mean ± standard deviation baseline age = 63.16 ± 7.20 y) from the Women's Health Initiative Clinical Trials and Women's Health Initiative Observational Study were analyzed. The cohort was followed for 15.88 ± 6.50 years, yielding 2,829 (2.17%) PD cases. Sleep disturbance (habitual sleep duration, insomnia symptoms, obstructive sleep apnea risk factors, sleep aids among those with WHI Insomnia Rating Scale scores (WHIIRS) > 9) was measured at baseline and one follow-up time by September 12, 2005. Cox proportional hazards models evaluated relationships controlling for sociodemographic, lifestyle, and health characteristics.

Results:

PD was significantly associated with long sleep duration (≥9 h) versus a benchmark of 7 to 8 hours (hazard ratio [HR] = 1.296, 95% confidence interval [CI]: 1.153-1.456), WHIIRS (>9 vs ≤9) (HR = 1.114, 95% CI:1.023-1.214), and use of sleep aids (yes vs no) (HR = 1.332, 95% CI:1.153-1.539) among those with WHIIRS > 9. Compared with 7 to 8 hours, short (<7 h) sleep duration was unrelated to PD. Finally, the presence of obstructive sleep apnea risk factors was not associated with PD.

Conclusions:

Among postmenopausal women, sleep disturbance was associated with approximately 10% to 30% increased PD risk after ∼16 years follow-up. Prospective cohort studies with objective exposures and adjudicated outcomes that include men and women of diverse backgrounds are required to confirm and extend these findings.
Current evidence for focal laser ablation and vascular-targeted photodynamic therapy for localized prostate cancer: review of literature published in the last 2 years
Authors: Candela Luigi , Kasraeian Ali , Barret Eric
Published: January 2022

Purpose of review

Currently, a significant number of patients are diagnosed with unilateral and apparently unifocal low or intermediate-risk prostate cancer (PCa). These patients are suitable for focal therapy, thus preventing radical treatment side effects without affecting cancer control. Among focal therapy energy sources, laser-based technologies have shown promising outcomes. We aimed to summarize recent data on focal laser ablation (FLA) and vascular-targeted photodynamic therapy (VTP) for PCa.

Recent findings

We selected eight studies reporting data on 1155 patients with PCa who underwent laser-based focal therapy. Five studies were on FLA and three on VTP (six prospective and two retrospective series); four reported both oncologic and functional outcomes whereas in three only oncologic and one only functional outcomes were discussed. Follow-up protocols and durations varied widely among the studies. PCa recurrence rates ranged between 20 and 56%. Urinary and erectile function were preserved after treatment, and complications were mild and transient. A lack of high-quality data on long-term oncological outcomes still remains, thus further highlighting the need for prospective controlled studies.

FLA and VTP are well tolerated procedures with excellent functional outcomes. However, both procedures showed a significant rate of PCa recurrence, thus demonstrating a certain grade of oncologic control failure of the procedure and/or nonoptimal patients’ selection.
Retrograde intrarenal surgery: laser showdown (Ho:YAG vs thulium fiber laser)
Authors: Corrales Mariela , Traxer Olivier
Published: January 2022

Purpose of review

Retrograde intrarenal surgery (RIRS) has always been recommended for large stones > 20 mm, using the Ho:YAG laser. The introduction of a new technology in the urological market, the thulium fiber laser (TFL) has revolutionized the endourology world because of its characteristics and significantly shorter laser-on time (LOT) and operative time, without scarifying the champ vision. The aim of this review is to evaluate the most relevant findings of the last 2 years of each laser technology, confronting Ho:YAG vs TFL, analyzing who is more suitable for performing an efficient RIRS.

Recent findings

Five full clinical trials using TFL for RIRS were found. Median LOT was between 2.8 and 34 min. All stones were similar in terms of stone volume, >500 mm3, and stone density, > 800 HU. Low complication rate, mostly Clavien-Dindo grade I and II and not related to the laser itself. One clinical trial only analyzed the efficacy of TFL for > 20 mm renal stones.

Based on this review, TFL performs a more efficient RIRS than the Ho:YAG laser with similar safety.
Managing fatigue at work after traumatic brain injury: a qualitative descriptive study
Authors: Lillas Sarah , Hay-Smith Jean , Levack William
Published: January 2022

Fatigue is a common sequela of traumatic brain injury (TBI) and adversely impacts on the ability to return to work. To the authors’ knowledge, no prior studies have investigated how people manage TBI-related fatigue at work. This qualitative descriptive study explored how people managed fatigue attributed to TBI when returning to and maintaining paid work. Eight employed adults, who sustained a recent TBI and experienced TBI-related fatigue, participated in a semi-structured interview. Transcripts were analysed using a general inductive approach. Participants learned through trial and error to recognise ‘change points’ – fatigue symptom awareness that prompted fatigue management. At each change point, participants selected the most effective strategy from a continuum of options to minimise the impact on productivity at work. This continuum may provide useful guidance to other people returning to and maintaining paid work while managing post-TBI fatigue symptoms.
Effect of COVID-19 stress on physical function performance and socioenvironmental factors of people with disabilities in Korea
Authors: Kim Jae-Hak , Rhee Hyun-Sill
Published: January 2022

This study investigated the effect of stress during the COVID-19 pandemic and the potential moderating effects of socioenvironmental factors on the physical conditions of Korean people with disabilities. Data from 405 participants on depression, instrumental activities of daily living and socioenvironmental factors were analyzed using frequency analysis, descriptive statistics, t-tests, one-way analysis of variance, Pearson’s correlations and hierarchical regression analysis. Stress caused by COVID-19 was significantly correlated with depression, instrumental activities of daily living and social participation. Using socioenvironmental factors as moderators of the relationship between stress and depression, we found that increased depression was alleviated by social attitudes (β = 2.064; P < 0.01), family attitudes (β = 2.028; P < 0.05) and healthcare services and policies (β = −4.579; P < 0.001). Moreover, instrumental activities of daily living increased with decreased stress as moderated by social attitudes (β = 0.140; P < 0.05) and healthcare services and policies (β = −0.306; P < 0.001). Further, increased social participation alleviated stress as moderated by social attitudes (β = 0.106; P < 0.01), mobility and convenience facilities (β = 0.158; P < 0.01) and healthcare services and policies (β = −0.342; P < 0.001). The results indicate that even in public healthcare crises, it is important for people with disabilities to manage their health and participate in social activities. Their self-management and social participation can be promoted by strengthening community-centered rehabilitation and providing consumer-oriented social services.
Reduced Levels of NAD in Skeletal Muscle and Increased Physiologic Frailty Are Associated With Viral Coinfection in Asymptomatic Middle-Aged Adults
Authors: Tran Thanh , Pencina Karol M. , Schultz Michael B. , Li Zhuoying , Ghattas Catherine , Lau Jackson , Sinclair David A. , Montano Monty
Published: January 2022

Background:

People living with HIV (PLWH) are disproportionately burdened with multimorbidity and decline in physiologic function compared with their uninfected counterparts, but biological mechanisms that differentially contribute to the decline in muscle function in PLWH compared with uninfected people remain understudied.

Setting:

The study site was Brigham and Women's Hospital, Harvard Medical School, Boston, MA.

Methods:

We evaluated skeletal muscle tissue for levels of total nicotinamide adenine dinucleotide (NAD), NAD+, and nicotinamide adenine dinucleotide (NADH) in middle-aged asymptomatic PLWH, coinfected with hepatitis C virus and/or cytomegalovirus and compared them with uninfected control participants.

Results:

Of the 54 persons with muscle biopsy data, the mean age was 57 years with 33% women. Total NAD levels declined in skeletal muscle in association with HIV infection and was exacerbated by hepatitis C virus and cytomegalovirus coinfection, with lowest levels of total NAD, NAD+, and NADH among persons who were coinfected with all 3 viruses (P = 0.015, P = 0.014, and P = 0.076, respectively). Levels of total NAD, NAD+, and NADH in skeletal muscle were inversely associated with inflammation (P = 0.014, P = 0.013, and P = 0.055, respectively). Coinfections were also associated with measures of inflammation (CD4/CD8 ratio: P < 0.001 and sCD163: P < 0.001) and immune activation (CD38 and human leukocyte antigen-DR expression on CD8 T cells: P < 0.001). In addition, coinfection was associated with increased physiologic frailty based on the Veteran Aging Cohort Study 1.0 index assessment (P = 0.001).

Conclusions:

Further research is warranted to determine the clinical relevance of preclinical deficits in NAD metabolites in skeletal muscle in association with viral coinfection and inflammation, as well as the observed association between viral coinfection and physiologic frailty.
Results of the Kigali Imbereheza Project: A 2-Arm Individually Randomized Trial of TI-CBT Enhanced to Address ART Adherence and Mental Health for Rwandan Youth Living With HIV
Authors: Donenberg Geri R. , Fitts Jessica , Ingabire Charles , Nsanzimana Sabin , Fabri Mary , Emerson Erin , Remera Eric , Manzi Olivier , Bray Bethany , Cohen Mardge H.
Published: January 2022

Background:

Adolescents living with HIV have elevated mental distress and suboptimal antiretroviral therapy (ART) adherence.

Setting:

Two urban clinics in Kigali, Rwanda.

Methods:

A 2-arm individual randomized controlled trial compared Trauma-Informed Cognitive Behavioral Therapy enhanced to address HIV (TI-CBTe) with usual care (time-matched, long-standing, unstructured support groups) with 356 12- to 21-year-old (M = 16.78) Rwandans living with HIV. TI-CBTe included 6 group-based 2-hour sessions led by trained and supervised 21- to 25-year-old Rwandans living with HIV. Participants reported their ART adherence, depression/anxiety, and Post-Traumatic Stress Disorder symptoms at baseline, 6, 12, and 18 months.

Results:

ART adherence was relatively high at baseline, and youth reported elevated rates of depression/anxiety and trauma symptoms. There were no differential treatment effects on adherence, but depression/anxiety improved over time. Youth with lower depression/anxiety at baseline seemed to benefit more from TI-CBTe than usual care, whereas women with high baseline distress seemed to benefit more from usual care. Youth were less likely to score in high Post-Traumatic Stress Disorder symptom categories at the follow-up, with no differential treatment effects.

Conclusions:

TI-CBTe did not outperform usual care on ART adherence, possibly reflecting relatively high adherence at baseline, simplified medication regimens over time, a strong comparison condition, or because youth assigned to TI-CBTe returned to their support groups after the intervention. TI-CBTe was more effective for youth with lower depression/anxiety symptoms, whereas youth with high distress benefitted more from the support groups. TI-CBTe was feasible and acceptable, and young adults living with HIV were able to deliver a mental health intervention with fidelity. The powerful nature of the comparison group, ongoing support groups, points to the potential value of locally crafted interventions in low-resource settings.