bluuebunny/crossref_metadata_2025 huggingface dataset:
Rituximab pediatric drug development: Pharmacokinetic and pharmacodynamic modeling to inform regulatory approval for rituximab treatment in patients with granulomatosis with polyangiitis or microscopic polyangiitis
Authors: Jamois Candice , Gibiansky Leonid , Chavanne Clarisse , Cheu Melissa , Lehane Patricia B. , Pordeli Pooneh , Melega Simone , Gaudreault Jacques
Published: June 2022

Anti‐neutrophil cytoplasmic antibody‐associated vasculitides granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are rare, potentially organ‐ and life‐threatening autoimmune conditions affecting adult and pediatric patients. An open‐label phase II study was conducted to determine safe and effective dosing regimens of rituximab in pediatric patients with GPA/MPA. To determine the selection of an appropriate dose regimen in children for induction and maintenance, a population pharmacokinetic approach was used (nonlinear mixed‐effect modeling), combining pediatric data with data from adults with GPA/MPA. The time course of B‐cell depletion was assessed in both populations. The exposure‐effect relationship was assessed by logistic regression. Twenty‐five pediatric patients (80% female patients; age range, 6–17 years) were enrolled in the trial and received the induction regimen of intravenous rituximab 375 mg/m2 weekly for 4 weeks, which resulted in a similar exposure to that of adults. Based on pharmacokinetic modeling, a maintenance dosing regimen of 250 mg/m2 administered twice over 14 days followed by 250 mg/m2 every 6 months is expected to result in similar rituximab exposure as that of adults receiving the approved maintenance dose of 500 mg administered twice over 14 days followed by 500 mg every 6 months. The time course of B‐cell depletion was similar between the pediatric and adult populations, supporting the similarities in response in both populations and allowing extrapolation to patients less than 6 years old. Using a partial extrapolation approach helped identify safe and effective dosing regimens of rituximab in pediatric patients with GPA/MPA and lead to regulatory approval.
Prescribing costs of hypoglycaemic agents and associations with metabolic control in Wales; a national analysis of primary care data
Authors: Taylor Peter N. , Siah Qi Zhuang , Marei Omar , McDade‐Kumar Mia , Rachedi Nasser , Bracchi Robert , Boldero Richard , Haines Kath , Ali Mohammed Alhadj , French Robert , Dayan Colin M.
Published: June 2022

Aims

There has been a dramatic increase in hypoglycaemic agent expenditure. We assessed the variability in prescribing costs at the practice level and the relationship between expenditure and the proportion of patients achieving target glycaemic control.

Methods

We utilized national prescribing data from 406 general practices in Wales. This was compared against glycaemic control (percentage of patients achieving a HbA1c level < 59 mmol/mol in the preceding 12 months). Analyses were adjusted for the number of patients with diabetes in each general practice and the Welsh Index of Multiple Deprivation.

Results

There was considerable heterogeneity in hypoglycaemic agent spend per patient with diabetes, Median = £289 (IQR 247–343) range £31.1–£1713. Higher total expenditure was not associated with improved glycaemic control B(std) = −0.01 (95%CI –0.01, 0.002) p = 0.13. High‐spend practices spent more on SGLT2 inhibitors (16 vs. 9% p < 0.001) and GLP‐1 agonists (13 vs. 11% p < 0.001) and less on insulin (34 vs. 42% p < 0.001), biguanides (9 vs. 11% p = 0.001) and sulphonylureas (2 vs. 3% p < 0.001) than low spend practices. There were no differences in the pattern of drug prescribing between high spend practices with better glycaemic control (mean 68% of patients HbA1c <59 mmol/mol) and those with less good metabolic control (mean 58% of patients HbA1c <59 mmol/mol).

Conclusions

Spend on hypoglycaemic agents is highly variable between practices and increased expenditure per patient is not associated with better glycaemic control. Whilst newer, more expensive agents have additional benefits, in individuals where these advantages are more marginal widespread use of these agents has important cost implications.
Political decentralization and corruption: Exploring the conditional role of parties
Authors: Shrestha Kshitiz , Martinez‐Vazquez Jorge , Hankla Charles
Published: June 2022

This study investigates how national levels of corruption are influenced by the interaction of two factors in political decentralization: the presence of local elections and the organizational structure of national parties. Previous studies have focused primarily on the role of fiscal decentralization on corruption and have mostly ignored the institutions of political decentralization. Using new data in a series of expansive models across multiple countries and years, we find that corruption will be lower when local governments are more accountable to and more transparent toward their constituents. This beneficial arrangement is most likely to occur when local elections are combined with nonintegrated political parties, meaning that party institutions themselves are decentralized from national control. Such an institutional arrangement maximizes local accountability by putting the decision to nominate and elect local leaders in the hands of those best in a position to evaluate their honesty—local electors.
Leaf blister on two Ericaceae plants infected by Exobasidium species in Japan
Authors: Shibata Saho , Tanaka Eiji , Hirooka Yuuri
Published: June 2022

Whitish blisters covered by a hymenium layer were found on the leaves of two Ericaceae plants, Vaccinium japonicum and Rhododendron lagopus var. niphophilum, in Shiramine, Ishikawa, Japan. Based on the morphological characteristics and molecular phylogenetic analyses, the pathogens found in V. japonicum and R. lagopus var. niphophilum were identified as Exobasidium rostrupii and Exobasidium yoshinagae, respectively. This is the first report of E. rostrupii and Exobasidium leaf blisters in two plants in Japan.
Circ_TLK1 knockdown alleviates oxygen–glucose deprivation/reoxygenation‐induced PC12 cell injury by regulating microRNA‐136‐5p/follistatin like‐1 axis
Authors: Zhang Zhenduo , He Jinbo , Wang Baoliang
Published: June 2022

Background

Circular RNAs (circRNAs) are aberrantly expressed in the central nervous system (CNS) and are involved in diverse CNS diseases. However, the functions of circRNAs in ischemic stroke (IS) are largely unknown. In this study, we aimed to explore the effect of circ_TLK1 in oxygen–glucose deprivation/reoxygenation (OGD/R)‐induced PC12 cell injury.

Methods

Quantitative real‐time polymerase chain reaction (qRT‐PCR) was performed for the levels of circ_TLK1, TLK1, microRNA‐136‐5p (miR‐136‐5p), and follistatin like‐1 (FSTL1). RNase R and Actinomycin D assays were conducted to analyze the features of circ_TLK1. 3‐(4, 5‐ethynyl‐2′‐deoxyuridine [EdU] assay and 5‐dimethyl‐2‐thiazolyl)‐2, 5‐diphenyl‐2‐H‐tetrazolium bromide (MTT) assay were adopted to analyze cell proliferation capacity. Flow cytometry analysis was applied to determine cell death. Western blot assay was employed to measure protein levels. The release of lactate dehydrogenase (LDH) was measured with specific kits. The interaction between circ_TLK1 and miR‐136‐5p, as well as miR‐136‐5p and FSTL1, was verified by Dual‐luciferase reporter assay.

Results

Circ_TLK1 was upregulated in OGD/R‐injured PC12 cells. OGD/R treatment inhibited cell proliferation, promoted cell death, and increased LDH release in PC12 cells, while circ_TLK1 knockdown partially alleviated OGD/R‐induced PC12 cell injury. Circ_TLK1 directly bound to miR‐136‐5p and miR‐136‐5p inhibition reversed the effect of circ_TLK1 knockdown on OGD/R‐induced PC12 cell damage. Moreover, FSTL1 was targeted by miR‐136‐5p. MiR‐136‐5p upregulation inhibited PC12 cell injury induced by OGD/R, while FSTL1 overexpression partially reversed the effect.

Conclusion

Circ_TLK1 knockdown ameliorated OGD/R‐induced PC12 cell injury by modulating miR‐136‐5p and FSTL1, which might provide a new understanding of IS treatment.
An experimental assessment of fracture toughness in novel crimp‐free‐based composite materials for aerospace applications
Authors: Lepore Marcello A. , Maligno Angelo R. , Canale Giacomo , Harris Linden
Published: June 2022

In the design of structural composite components for aerospace applications, durability and reliability play a very significant role. To assess the reliability of these material it is essential to carry out robust experimental tests on several specimens and under different loading conditions to allow the determination of fundamental fracture parameters. Fracture toughness, in particular, allows the quantification of the material strength to fracture. This work proposes a study on non‐crimp fabric (NCF) together with a two‐component epoxy resin. The selected system has been selected based on its suitability to produce aerospace‐approved components using resin transfer molding (RTM) process. The fabric adopted is a SAERTEX NCF with very high modulus and strength, whereas the resin is BDP 4294. This work shows the methods, equipment, and results of an experimental campaign carried out to determine the fracture toughness of the manufactured NCF composite material. Finally, to quantify the fracture toughness of the NCF composite material, Mode I, II, Mixed Mode I–II, and translaminar fracture tests were also considered.
Intensive care in an older population: Influence of age, comorbidities and sex in 304 plastic and reconstructive surgical patients older than 75 years
Authors: Staud Clement J. , Zaussinger Maximilian , Holzbauer Matthias , Christ Alexandra , Beiglböck Hannes , Unterberger Karin , Radtke Christine
Published: June 2022

Aim

An aging population will lead to an increasing demand for critical care resources. Hence, we evaluated the potential influence of age, comorbidities and sex in plastic and reconstructive patients ≥75 years that were admitted to the intensive care unit (ICU).

Methods

We included 304 patients who required intensive care between 2000 and 2019. Besides patient demographics, medical case characteristics were statistically evaluated.

Results

In this study, 184 patients were female (61%) (120 male), the median age was 81.8 years (25th and 75th percentiles: 77.4–87.2) with a range of 75.0–98.9 years. The median length of stay in the ICU was 12 days (25th and 75th percentiles: 3–28) with a range of 0–382 days. The reasons for admission were burn injury (n = 230, 76%), necrotizing fasciitis (n = 34, 11%), non‐combustion‐related traumas (n = 22, 7%) and postoperative observation after plastic surgery procedures (n = 18, 6%). In total, 108 patients (36%), who were significantly older (P = 0.005) and had a significantly shorter stay (P < 0.001) compared with the surviving cohort, died during their stay in the ICU. Our multivariable logistic regression model revealed that age (odds ratio: 1.05 [1.01, 1.09]; P = 0.017) and number of operations (odds ratio: 0.75 [0.60, 0.96]; P = 0.023) were significant predictors for death in the ICU.

Discussion

Age plays a critical role in determining fatal outcome of old patients requiring intensive care. In contrast, sex and number of comorbidities shows no significant influence. Geriatr Gerontol Int 2022; 22: 597–602.
Robot‐assisted versus conventional laparoscopic partial nephrectomy for renal hilar tumors: Parenchymal preservation and functional recovery
Authors: Bao Xingjun , Dong Wen , Wang Jipeng , Sun Fengze , Yao Huibao , Wang Di , Zhou Zhongbao , Wu Jitao
Published: June 2022

Objective

To determine whether robot‐assisted laparoscopic partial nephrectomy (RALPN) can benefit patients in terms of functional recovery in the treatment of renal hilar tumors compared to conventional laparoscopic partial nephrectomy (CLPN).

Methods

Between January 2019 and July 2021, patients with hilar tumors who underwent partial nephrectomy (PN) were acquired at our center and were classified into RALPN and CLPN groups. Ipsilateral parenchymal volume (IPV) and glomerular filtration rate (GFR) were determined independently 3–5 days before and 3 months after PN using contrast‐enhanced computed tomography and nuclear renal scans. Pearson correlation was used to determine the link between ipsilateral GFR preservation and IPV preserved. Concurrently, multivariable analysis was employed to determine characteristics associated with functional recovery.

Results

A total of 96 patients with hilar tumors were studied, of which 41 received RALPN and 55 received CLPN. Excisional parenchymal volume was 27 and 37 cm3 (p = 0.005) in RALPN and CLPN groups, respectively, and IPV preserved was 77% and 68% (p < 0.001). Furthermore, the ipsilateral GFR preserved was 77.7% and 75.3%, respectively (p = 0.003). On Pearson correlation, ipsilateral GFR preservation was linked with IPV preserved (r = 0.36, p < 0.001). According to a multivariate study, baseline GFR, IPV preserved, and surgical procedures (RALPN vs. CLPN) were significant factors influencing functional recovery.

Conclusion

Our study suggests that RALPN, rather than CLPN, can achieve better functional recovery in the treatment of hilar tumors due to its ability to win more IPV preserved. RALPN should be recommended as the first‐line treatment for hilar tumors, but randomized controlled trials are required to validate our findings.
Longing for homelikeness: A hermeneutic phenomenological analysis of patients' lived experiences in recovery from COVID‐19‐associated intensive care unit acquired weakness
Authors: van Oorsouw Roel , Klooster Emily , Koenders Niek , Van Der Wees Philip J. , Van Den Boogaard Mark , Oerlemans Anke J. M.
Published: June 2022

Aims

To explore lived experiences of patients recovering from COVID‐19‐associated intensive care unit acquired weakness and to provide phenomenological descriptions of their recovery.

Design

A qualitative study following hermeneutic phenomenology.

Methods

Through purposeful sampling, 13 participants with COVID‐19‐associated intensive care unit acquired weakness were recruited with diversity in age, sex, duration of hospitalization and severity of muscle weakness. Semi‐structured in‐depth interviews were conducted from 4 to 8 months after hospital discharge, between July 2020 and January 2021. Interviews were transcribed verbatim and analysed using hermeneutic phenomenological analysis.

Results

The analysis yielded five themes: ‘waking up in alienation’, ‘valuing human contact in isolation’, ‘making progress by being challenged’, ‘coming home but still recovering’ and ‘finding a new balance’. The phenomenological descriptions reflect a recovery process that does not follow a linear build‐up, but comes with moments of success, setbacks, trying new steps and breakthrough moments of achieving mobilizing milestones.

Conclusion

Recovery from COVID‐19‐associated intensive care unit acquired weakness starts from a situation of alienation. Patients long for familiarity, for security and for recognition. Patients want to return to the familiar situation, back to the old, balanced, bodily self. It seems possible for patients to feel homelike again, not only by changing their outer circumstances but also by changing the understanding of themselves and finding a new balance in the altered situation.

Impact

Muscle weakness impacts many different aspects of ICU recovery in critically ill patients with COVID‐19‐associated intensive care unit acquired weakness. Their narratives can help nurses and other healthcare professionals, both inside and outside of the intensive care unit, to empathize with patient experiences. When healthcare professionals connect to the lifeworld of patients, they will start to act and communicate differently. These insights could lead to optimized care delivery and meeting patients' needs in this pandemic or a possible next.
Newtonian science, complexity science and suicide—critically analysing the philosophical basis for suicide research: A discussion paper
Authors: Olarte‐Godoy Jennifer
Published: June 2022

Aim

A critical discussion comparing Newtonian science and complexity science as the philosophical basis for suicide research and its impact on suicide knowledge development and clinical practice.

Design

Discussion paper.

Data Sources

A review of literature on suicide research and complexity science ranging from 2000 to 2022.

Implications for Nursing

Suicide research based on a Newtonian worldview can have negative consequences for suicide knowledge development and can permeate nursing practice in ways that take away from addressing the complex needs of patients, their families and healthcare teams.

Conclusion

A Newtonian worldview as a philosophical basis for research is insufficient for the study of a phenomenon as complex as suicide. A complexity science approach is better suited to the study of suicide given the multiple, interrelated, emerging factors that can contribute to a person's decision to end their own life.

Impact

Suggestions are provided as to how a complexity science approach to the research of suicide can inform useful knowledge development that better meets the needs of individuals facing suicidality and their families. Researchers, healthcare administrators and nurses providing care to those struggling with suicidality can benefit from adopting a complexity science worldview in addressing this multifaceted phenomenon.
Psychometric properties of the Turkish version of the Readiness to Encounter Partner Abuse Patients Scale
Authors: Çürük Gülsüm Nihal , Özgül Ecem , Alkanat Hafize Özdemir
Published: June 2022

Aim

Partner abuse is a global public health issue with both short‐ and long‐term health effects. Healthcare professionals frequently encounter patients who experience partner abuse and should be knowledgeable about how to respond to these individuals. The aim of this study was to examine the validity and reliability of the Turkish version of The Readiness to Encounter Partner Abuse Patients (READI) Scale.

Design

A descriptive, methodological and cross‐sectional design was used.

Methods

Data were collected with a sociodemographics form and the READI‐T Scale between 13 December 2021 and 5 January 2022. The study sample comprised nursing students (n = 323) at or over the age of 18 years and accepting to take part in the study. The linguistic and content validity and confirmatory factor analysis were used to assess the validity of the scale. The reliability of the scale was achieved using Cronbach's alpha, item‐total correlations and test–retest.

Results

The READI‐T Scale had a content validity index of 0.99 and adequate sensitivity. The factor loadings ranged from 0.63 to 0.84 for the self‐efficacy sub‐dimension, from 0.82 to 0.91 for the emotional readiness sub‐dimension, from 0.47 to 0.81 for the motivational readiness sub‐dimension and from 0.28 to 0.64 for the partner abuse knowledge sub‐dimension. The CFA showed that the model had a good fit (x2/df = 1.792; GFI = 0.88; CFI = 0.94; RMSEA = 0.050). Cronbach's alpha was found to be 0.92 for the scale.

Conclusion

The READI‐T Scale is a valid and reliable tool to determine whether Turkish nursing students are knowledgeable enough to encounter partner abuse patients.

Impact

This scale can be used to determine the training needs of healthcare professionals on partner abuse and may be useful as a pre‐and posttest to determine the effects of partner abuse education programs. Thus, this scale may also assist early identification of persons who have a risk for partner abuse.
Effects of smoking intensity trajectory, cumulative smoking exposure, and the number of years since quitting on the subsequent risk of hypertension
Authors: Fan Hui , Zhang Xingyu
Published: June 2022

The aim of this study was to investigate the effects of smoking intensity trajectory, cumulative smoking exposure, and the number of years since quitting on the subsequent risk of hypertension in Chinese adults. The study included 2783 men and 3416 women who participated in at least three waves of the China Health and Nutrition Survey. Information regarding smoking behavior was obtained using a standardized questionnaire. The trajectory of smoking intensity was determined using a group‐based trajectory model. The number of pack‐years of smoking and the number of years since quitting were calculated. The incidence of hypertension was 18.2% and 15.5% in men and women, respectively, during a median follow‐up duration of 4 years. Male participants with trajectories denoting light and moderate smoking had increased risks of hypertension compared with those with trajectories denoting non‐smoking (Ps < .05). Compared with male participants with 0 pack‐years, those with < 5.5 pack‐years had a higher risk of hypertension (P < .05). Male participants with ≥5.5 pack‐years and weight gain had a higher risk of hypertension compared with those with 0 pack‐years and weight loss (P < .05). However, smoking was not related to an increased risk of hypertension in women. Additionally, similar to never smoking, having quit within 2–5 years or ≥5 years was not associated with the incidence of hypertension in men. The results of this study showed that light/moderate smoking or high cumulative smoking exposure accompanied by weight gain increased the risk of hypertension in Chinese men and smoking cessation decreased this effect.
Gene–environment interplay in externalizing behavior from childhood through adulthood
Authors: Kretschmer Tina , Vrijen Charlotte , Nolte Ilja Maria , Wertz Jasmin , Hartman Catharina Annette
Published: June 2022

Background

Genetic and environmental influences on externalizing problems are often studied separately. Here, we extended prior work by investigating the implications of gene–environment interplay in childhood for early adult externalizing behavior. Genetic nurture would be indicated if parents' genetic predisposition for externalizing behavior operates through the family environment in predicting offspring early adult externalizing behavior. Evocative gene–environment correlation would be indicated if offspring genetic predisposition for externalizing behavior operates through child externalizing behavior in affecting the family environment and later early adult externalizing behavior.

Method

Longitudinal data from seven waves of the TRacking Adolescents' Individual Lives Survey, a prospective cohort study of Dutch adolescents followed from age 11 to age 29 (n at baseline = 2,734) were used. Child externalizing behavior was assessed using self and parent reports. Family dysfunction was assessed by parents. Early adult externalizing behavior was assessed using self‐reports. Genome‐wide polygenic scores for externalizing problems were constructed for mothers, fathers, and offspring.

Results

Offspring polygenic score and child behavior each predicted early adult externalizing problems, as did family dysfunction to a small extent. Parents' polygenic scores were not associated with offspring's early adult externalizing behavior. Indirect effect tests indicated that offspring polygenic score was associated with greater family dysfunction via child externalizing behavior (evocative gene–environment correlation) but the effect was just significant and the effect size was very small. Parents' polygenic scores did not predict family dysfunction, thus the data do not provide support for genetic nurture.

Conclusions

A very small evocative gene–environment correlation was detected but effect sizes were much more pronounced for stability in externalizing behavior from childhood through early adulthood, which highlights the necessity to intervene early to prevent later problems.
Commentary: The global prevalence of depression and anxiety symptoms among college students and its influencing factors – a commentary on Li et al. (2022)
Authors: Zhang Haozhe , Wang Dongming
Published: June 2022

The commentary cites a study by Li and colleagues (2022) that conducted a comprehensive study of depression and anxiety symptoms among college students worldwide. We highlight the valuable contribution of this work to ongoing research, policy, and practice related to the early diagnosis and prevention of depression and anxiety symptoms in college students. The comprehensive report compensates for the lack of similar comprehensive studies in relevant areas and draws attention to the limitations of this and similar studies that require new solutions if well‐designed, theoretically robust and implementable interventions are to be advanced. The author's work is timely and persuasive, providing important insights and theoretical support for specific work in the field of mental health of college students.
UpdatedS2K guidelines for the management of bullous pemphigoid initiated by the European Academy of Dermatology and Venereology (EADV)
Authors: Borradori L. , Van Beek N. , Feliciani C. , Tedbirt B. , Antiga E. , Bergman R. , Böckle B. C. , Caproni M. , Caux F. , Chandran N.S. , Cianchini G. , Daneshpazhooh M. , De D. , Didona D. , Di Zenzo G. M. , Dmochowski M. , Drenovska K. , Ehrchen J. , Goebeler M. , Groves R. , Günther C. , Horvath B. , Hertl M. , Hofmann S. , Ioannides D. , Itzlinger‐Monshi B. , Jedličková J. , Kowalewski C. , Kridin K. , Lim Y. L. , Marinovic B. , Marzano A. V. , Mascaro J.‐M. , Meijer J.M. , Murrell D. , Patsatsi K. , Pincelli C. , Prost C. , Rappersberger K. , Sárdy M. , Setterfield J. , Shahid M. , Sprecher E. , Tasanen K. , Uzun S. , Vassileva S. , Vestergaard K. , Vorobyev A. , Vujic I. , Wang G. , Wozniak K. , Yayli S. , Zambruno G. , Zillikens D. , Schmidt E. , Joly P.
Published: June 2022

Background

Bullous pemphigoid (BP) is the most common autoimmune subepidermal blistering disease of the skin and mucous membranes. This disease typically affects the elderly and presents with itch and localized or, most frequently, generalized bullous lesions. A subset of patients only develops excoriations, prurigo‐like lesions, and eczematous and/or urticarial erythematous lesions. The disease, which is significantly associated with neurological disorders, has high morbidity and severely impacts the quality of life.

Objectives and methodology

The Autoimmune blistering diseases Task Force of the European Academy of Dermatology and Venereology sought to update the guidelines for the management of BP based on new clinical information, and new evidence on diagnostic tools and interventions. The recommendations are either evidence‐based or rely on expert opinion. The degree of consent among all task force members was included.

Results

Treatment depends on the severity of BP and patients' comorbidities. High‐potency topical corticosteroids are recommended as the mainstay of treatment whenever possible. Oral prednisone at a dose of 0.5 mg/kg/day is a recommended alternative. In case of contraindications or resistance to corticosteroids, immunosuppressive therapies, such as methotrexate, azathioprine, mycophenolate mofetil or mycophenolate acid, may be recommended. The use of doxycycline and dapsone is controversial. They may be recommended, in particular, in patients with contraindications to oral corticosteroids. B‐cell‐depleting therapy and intravenous immunoglobulins may be considered in treatment‐resistant cases. Omalizumab and dupilumab have recently shown promising results. The final version of the guideline was consented to by several patient organizations.

Conclusions

The guidelines for the management of BP were updated. They summarize evidence‐ and expert‐based recommendations useful in clinical practice.
Temporal increase of Varroa mites in trap frames used for drone brood removal during the honey bee season
Authors: Odemer Richard , Odemer Franziska , Liebig Gerhard , de Craigher Doris
Published: June 2022

Varroa mites are highly attracted to drone brood of honey bees (Apis mellifera), as it increases their chance of successful reproduction. Therefore, drone brood removal with trap frames is common practice among beekeepers in Europe and part of sustainable varroa control. However, it is considered labour‐intensive, and there are doubts about the effectiveness of this measure. At present, it is mostly unknown how many mites a drone frame can carry at different times of the season, and how many mites can be removed on average if this measure is performed frequently. Therefore, we sampled a total of 262 drone frames with varying proportion of capped cells (5–100%) from 18 different apiaries. Mites were washed out from brood collected from mid‐April to mid‐July based on a standard method to obtain comparable results. We found that a drone frame carried a median of 71.5 mites, and with the removal of four trap frames, about 286 mites can be removed per colony and season. In addition, mite counts were significantly higher in June and July than in April and May (Tukey‐HSD, P < 0.05). The number of mites and the proportion of capped cells, however, were not correlated (R2 < 0.01, P < 0.05). Our results suggest that drone brood removal is effective in reducing Varroa destructor numbers in colonies, supporting the findings of previous studies on the efficacy of this measure. Although mite counts varied, we believe that increasing sample size over different seasons and locations could elucidate infestation patterns in drone brood and ultimately improve drone brood removal as an integrated pest management tool for a wider audience of beekeepers.
The credit channel of monetary policy before and after the zero lower bound: Evidence from the US equity market
Authors: Farka Mira
Published: June 2022

I evaluate the effectiveness of conventional and unconventional monetary policy measures by examining the transmission mechanism through the credit channel before and after the zero lower bound (ZLB). I focus on the impact of conventional and unconventional policy shocks on a cross‐section of portfolio returns sorted on characteristics that capture firms' financial constraints (size and book‐to‐market). Results show that the credit channel of monetary policy is even more relevant at the ZLB relative to the previous period, and its effectiveness is almost entirely attributed to the high sensitivity of financially constrained firms (small and value stocks) to unconventional surprises. I find strong evidence that the reaction of portfolio returns to policy shocks is asymmetric depending on the state of the economy (recession vs. expansion), type of policy surprise (positive vs. negative), and aggregate level of market volatility. My findings are robust to several model extensions and alternative specifications.
Parental consideration of children's experiences: A critical review of parenting constructs
Authors: Joussemet Mireille , Grolnick Wendy S.
Published: June 2022

The purpose of this paper is to bring together and highlight common conceptual elements and findings from constructs that involve parents' consideration of children's viewpoints and experiences: parental sensitivity, empathy, perspective taking, responsiveness, autonomy support, and scaffolding. Research on each of these constructs suggests that consideration in the parenting role is associated with better child development, learning, and well‐being. We examine definitions and measures of the constructs to address how parental consideration has been conceptualized. We also review positive child development indicators that have been associated with it, across various periods, contexts, and domains of development. By drawing attention to this common denominator and adopting an integrative perspective, we hope to contribute to future research and help transfer knowledge to parents about this key, facilitative parenting dimension.
Dementia prevalence, a contextual factor associated with SARS‐CoV‐2 in veterans affairs community living centers
Authors: Bayer Thomas A. , DeVone Frank , McConeghy Kevin W. , Halladay Christopher W. , Quach Lien , Rajan Ashna , Elhamamsy Salaheldin , Cadieux Marilyne , Singh Mriganka , Sachar Moniyka , Nanda Aman , Gravenstein Stefan , Rudolph James L.
Published: June 2022

Background

Alzheimer's disease and related dementias (ADRD) impact the diagnosis and infection control of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) in nursing homes (NH) by influencing the behavior of residents and their caregivers. Health system data show an association between ADRD and SARS‐CoV‐2. Whether this association is present in NH populations remains unknown. How increased SARS‐CoV‐2 risk among residents with ADRD impacts the greater NH population also remains unknown.

Methods

This retrospective cohort study used electronic health record data on Veterans residing in 133 Veterans Affairs Community Living Centers (CLC) and 15 spinal cord injury units from March 1, 2020 to December 13, 2020. We measured ADRD using diagnostic codes 12 months before an index SARS‐CoV‐2 test date for each resident. We used Poisson regression to determine the relative risk of SARS‐CoV‐2 for the highest quartile of facility ADRD prevalence versus the lowest, stratifying by individual ADRD status, and adjusting for covariates, with and without a random intercept to account for facility clustering.

Results

Across the study period, 15,043 residents resided in CLCs, 1952 (13.0%) had SARS‐CoV‐2, and 8067 (53.6%) had ADRD. There was an estimated 60% increased risk of SARS‐CoV‐2 in facilities with highest dementia prevalence versus lowest (relative risk, 1.6 [95% confidence interval 0.95, 2.7]).

Conclusions

CLC residents had a greater likelihood of SARS‐CoV‐2 infection in facilities with greater ADRD prevalence. Facility characteristics other than ADRD prevalence may account for this association.
The divergence of brassinosteroid sensitivity between rice subspecies involves natural variation conferring altered internal auto‐binding of OsBSK2
Authors: Yin Wenchao , Li Lulu , Yu Zhikun , Zhang Fan , Liu Dapu , Wu Hongkai , Niu Mei , Meng Wenjing , Zhang Xiaoxing , Dong Nana , Yang Yanzhao , Liu Jihong , Liu Yongqiang , Zhang Guoxia , Xu Jianlong , Wang Shimei , Chu Chengcai , Qian Qian , Tong Hongning
Published: June 2022

Japonica/geng and indica/xian are two major rice (Oryza sativa) subspecies with multiple divergent traits, but how these traits are related and interact within each subspecies remains elusive. Brassinosteroids (BRs) are a class of steroid phytohormones that modulate many important agronomic traits in rice. Here, using different physiological assays, we revealed that japonica rice exhibits an overall lower BR sensitivity than indica. Extensive screening of BR signaling genes led to the identification of a set of genes distributed throughout the primary BR signaling pathway with divergent polymorphisms. Among these, we demonstrate that the C38/T variant in BR Signaling Kinase2 (OsBSK2), causing the amino acid change P13L, plays a central role in mediating differential BR signaling in japonica and indica rice. OsBSK2L13 in indica plays a greater role in BR signaling than OsBSK2P13 in japonica by affecting the auto‐binding and protein accumulation of OsBSK2. Finally, we determined that OsBSK2 is involved in a number of divergent traits in japonica relative to indica rice, including grain shape, tiller number, cold adaptation, and nitrogen‐use efficiency. Our study suggests that the natural variation in OsBSK2 plays a key role in the divergence of BR signaling, which underlies multiple divergent traits between japonica and indica.
Tectonic erosion and deep subduction in Central Tibet: Evidence from the discovery of retrograde eclogites in the Amdo microcontinent
Authors: Peng Yinbiao , Yu Shengyao , Li Sanzhong , Liu Yongjiang , Santosh M. , Lv Pei , Li Yunshuai , Li Chuanzhi , Liu Yiming
Published: June 2022

The Amdo microcontinent which separates the Qiangtang terrane to the north and the Lhasa terrane to the south is a key terrane for reconstructing the tectonic evolution of Central Tibet. We report the new finding of retrograde eclogites within the Amdo microcontinent in this study. The eclogites are characterized by peak metamorphic mineral assemblages of garnet, omphacite, rutile and quartz and underwent a four‐stage metamorphic evolution, including a peak eclogite facies stage (M1) at ~20–24 kbar and 580–620°C, followed by an HP granulite facies decompression stage (M2) at ~13–15 kbar and 750–780°C, a subsequent MP‐UHT granulite facies heating stage (M3) at 8–10 kbar and >840°C and a final amphibolite facies retrogression (M4) at 5.3–6.0 kbar and 560–580°C. The eclogites exhibit rare earth element distribution patterns and trace element abundances similar to those of N‐MORB and arc‐related volcanics, with depleted whole‐rock εNd(t) values of 3.4 to 4.2, and are inferred to have formed in a back‐arc basin tectonic setting. Zircon and rutile U–Pb dating yields a protolith age of 226 ± 5 Ma, a peak eclogite facies metamorphic age of 190 ± 1 Ma, an HP granulite facies metamorphic age of 179 ± 1 Ma and an amphibolite facies retrograde age of 172 ± 1 Ma. The clockwise P–T–t paths and the oceanic protolith signature of retrograde eclogites suggest that part of the back arc basin was subducted to depths of ~80 km. Tectonic erosion associated with the subduction of the Amdo microcontinent beneath the Tethys Ocean accounts for the deep subduction of the back‐arc basin and the absence of arc magmatic rocks in the northern Amdo microcontinent.
Investigating the association of mood and fatigue with objective and subjective cognitive impairment in multiple sclerosis
Authors: Davenport Laura , Cogley Clodagh , Monaghan Ruth , Gaughan Maria , Yap Mei , Bramham Jessica , Tubridy Niall , McGuigan Chris , O'Keeffe Fiadhnait
Published: June 2022

Discrepancies between subjective cognitive difficulties and objective measures of cognitive function in people with MS have been identified and may be related to mood and fatigue. The aim of the present study was to examine associations of depression and fatigue with discrepancies between subjective and objective cognitive functioning in pwMS. 177 participants with MS attending a University Hospital Department of Neurology MS Outpatient clinic completed the Brief International Cognitive Assessment for MS (BICAMS), MS Neuropsychological Questionnaire (MSNQ), Hospital Anxiety and Depression Scale (HADS) and Modified Fatigue Impact Scale (MFIS). To quantify the discrepancy between objective (BICAMS) and subjective (MSNQ) cognitive functioning, discrepancy scores were calculated by subtracting MSNQ z‐score from composite BICAMS z‐score. Based on their discrepancy score, participants were grouped as ‘Underestimated’, ‘Overestimated’ and ‘Non‐discrepant’. 39% of the total sample demonstrated poorer subjective cognitive functioning than their objective cognitive performance suggested (‘Underestimated’). 23% of the total sample indicated lower objective scores than their subjective report suggests (‘Overestimated’). 38% participants indicated relatively no discrepancy between objective and subjective cognitive measures (‘Non‐discrepant’). Significant differences were observed between the discrepancy groups in terms of depression and fatigue, with the ‘Underestimated’ group demonstrating greater levels of depression and fatigue (ps < .01). Regression analysis indicated that cognitive fatigue and depression significantly contributed to variance in subjective cognitive functioning. Our findings suggest that subjective reports of cognitive function may be influenced by depression and fatigue, emphasising the importance of cognitive, mood and fatigue screening as part of routine clinical care.
The regulatory role of HOX interacting lncRNA in oral cancer—An in silico analysis
Authors: Basavarajappa Dhanraj Salur , Padam Kanaka Sai Ram , Chakrabarty Sanjiban , AN Naveena Kumar , Radhakrishnan Raghu
Published: June 2022

Objectives

We aim to elucidate the interaction of long noncoding RNAs with HOX genes and their regulatory role and potential drug candidates in oral cancer.

Materials and Methods

The interaction network was constructed using RNA Interactome and the RNA Interactome from the Sequencing Experiments database. The differential expression of HOX genes and HOX interacting lncRNAs was assessed using the TCGA‐Head and Neck Squamous Cell Carcinoma oral cancer dataset using DESeq2 R‐package. Further, the functional enrichment analysis was performed for the differentially expressed HOX genes and HOX‐interacting lncRNAs using Gene Ontology, long noncoding RNA Set Enrichment Analysis, lncRNA ontology annotation extractor and repository (Lantern), and LncRNA Ontology tools. Drug‐lncRNA interaction and the effect of drugs on lncRNA expression were assessed from the D‐lnc tool.

Results

A total of 78 unique interactions were identified between HOX and lncRNAs. Differential expression analysis showed 27 HOX genes and 10 HOX‐interacting lncRNAs in oral cancer. HOX genes and HOX‐interacting lncRNAs were involved in crucial regulatory processes like cell cycle regulation, cell proliferation and migration, epithelial‐mesenchymal transition, angiogenesis, and cell signaling pathways. Cancer hallmark analysis from using long noncoding RNA Set Enrichment Analysis showed the involvement of HOTAIR, HOTTIP MIR503HG, and CDKN2B‐AS1 in proliferation, migration, and invasion. Panobinostat was the common drug that influenced the expression of HOTAIR, HOTAIRM1, HOTTIP and CDKN2B‐AS1.

Conclusions

Differentially expressed HOX‐interacting lncRNAs are involved in various regulatory biological processes and cancer hallmark events in oral cancer.

Clinical Relevance

The creation of interaction networks may expand the existing knowledge of oral cancer signaling pathways and the discovery of novel targets.
Antibody deposition on vascular endothelial cells contributes to localized inflammation in salivary glands
Authors: Bagavant Harini , Trzeciak Marta , Biswas Indranil , Papinska Joanna A. , Cizio Katarzyna , Deshmukh Umesh S.
Published: June 2022

Background

Oral and ocular dryness due to reduced saliva and tear production, exocrine gland inflammation, and autoantibodies to multiple cellular proteins are the cardinal features of Sjögren's Disease. Among the autoantibody specificities, anti‐Ro52 is linked with higher disease severity. We have previously reported that mice immunized with recombinant Ro52 developed IgG deposits in salivary and lacrimal glands and showed reduced saliva and tear production. Furthermore, passive transfer of sera from Ro52‐immunized mice rapidly induced glandular dysfunction without immune cell infiltration in recipient mice.

Methods

To identify mechanisms driving antibody‐mediated salivary gland dysfunction, hyperimmune rabbit antiserum to mouse Ro52 was passively transferred into NZM2758 female mice, pretreated with alum adjuvant. Alum‐pretreated mice given hyperimmune rabbit antiserum to maltose‐binding protein served as controls. Antibody deposition and its distribution in the salivary glands were studied by immunofluorescence staining for rabbit IgG, nerve fibers, and endothelial cells. The nCounter inflammation panel was used to determine differentially expressed genes in the salivary gland.

Results

Rabbit IgG deposits were detected in salivary glands of anti‐Ro52 immune sera recipients. The rabbit IgG was present on the endothelial cells in small blood vessels, and it did not co‐localize with nerve fibers. Ingenuity pathway analysis of the gene expression dataset predicted the canonical vascular endothelial growth factor (VEGF) pathway as the most activated and Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) as the most inhibited pathway in the salivary glands of anti‐Ro52 sera recipients.

Conclusion

Our study suggests that autoantibody deposition on salivary gland endothelial cells might play a critical role in the pathogenesis of Sjögren's Disease.
Chasing up and locking down the virus: Optimal pandemic interventions within a network
Authors: Freiberger Michael , Grass Dieter , Kuhn Michael , Seidl Andrea , Wrzaczek Stefan
Published: June 2022

During the COVID‐19 pandemic countries invested significant amounts of resources into its containment. In early stages of the pandemic most of the (nonpharmaceutical) interventions can be classified into two groups: (i) testing and identification of infected individuals, (ii) social distancing measures to reduce the transmission probabilities. Furthermore, both groups of measures may, in principle, be targeted at certain subgroups of a networked population. To study such a problem, we propose an extension of the SIR model with additional compartments for quarantine and different courses of the disease across several network nodes. We develop the structure of the optimal allocation and study a numerical example of three symmetric regions that are subject to an asymmetric progression of the disease (starting from an initial hotspot). Key findings include that (i) for our calibrations policies are chosen in a “flattening‐the‐curve,” avoiding hospital congestion; (ii) policies shift from containing spillovers from the hotspot initially to establishing a symmetric pattern of the disease; and (iii) testing that can be effectively targeted allows to reduce substantially the duration of the disease, hospital congestion and the total cost, both in terms of lives lost and economic costs.
Transplantation of hepatitis D virus patients: Lifelong hepatitis B immunoglobulins?
Authors: Ferenci Peter , Reiberger Thomas , Stadlbauer Vanessa , Zoller Heinz
Published: June 2022

The introduction of Hepatitis B Immunoglobulins (HBIg) prophylaxis at and after liver transplantation (LT) facilitated excellent long‐term survival of transplant patients with chronic hepatitis B virus (HBV) infection. Several studies suggested that only short‐term (i.e. 4–8 weeks) HBIg prophylaxis after LT followed by the long‐term administration of HBV polymerase inhibitors prevents HBV recurrence. In hepatitis D virus (HDV)/HBV co‐infected patients, the need for long‐term HBIg prophylaxis on top of HBV polymerase inhibitors is unknown. HDV requires HBV surface antigen (HBsAg) for uptake into hepatocytes to subsequently establish HDV replication. Data on HDV recurrence and its impact on outcomes after LT are limited. In this review, we evaluated the available data on post‐LT recurrence of HBV and/or HDV. Overall, HBIg prophylaxis was effective, but 10–13% of patients became HBsAg positive after LT. Only a single study from Turkey reported HDV recurrence, which was not observed in other LT centres. Since all studies administered continuous HBIg prophylaxis, the post‐LT recurrence rates without HBIg prophylaxis remain unknown. In a German study, the clinical course and histopathological aspects of liver injury (inflammation, fibrosis and steatosis) were similar in post‐LT patients on continuous HBIg and those who stopped HBIg after a median of 72 months. Discontinuation of HBIg in stable patients after LT for HBV/HDV co‐infection did not lead to impaired overall survival or a higher recurrence rate in this long‐term follow‐up. In summary, discontinuation of HBIg after liver transplantation for HBV/HDV liver disease seems safe, but randomized controlled studies are needed before it can be generally recommended.