bluuebunny/crossref_metadata_2025 huggingface dataset:
Higher number of tacrolimus dose adjustments in kidney transplant recipients who are extensive and intermediate CYP3A5 metabolizers
Authors: Reininger Kevin A. , Onyeaghala Guillaume , Anderson‐Haag Teresa , Schladt David S. , Wu Baolin , Guan Weihua , Dorr Casey R. , Remmel Rory P. , Mannon Roslyn , Matas Arthur J. , Oetting William S. , Stahler Paul , Israni Ajay K. , Jacobson Pamala A.
Published: December 2022

Kidney transplant recipients carrying the CYP3A5*1 allele have lower tacrolimus troughs, and higher dose requirements compared to those with the CYP3A5*3/*3 genotype. However, data on the effect of CYP3A5 alleles on post‐transplant tacrolimus management are lacking. The effect of CYP3A5 metabolism phenotypes on the number of tacrolimus dose adjustments and troughs in the first 6 months post‐transplant was evaluated in 78 recipients (64% Caucasians). Time to first therapeutic concentration, percentage of time in therapeutic range (TTR), and estimated glomerular filtration rate (eGFR) were also evaluated. Fifty‐five kidney transplant recipients were CYP3A5 poor metabolizers (PM), 17 were intermediate metabolizers (IM), and 6 were extensive metabolizers (EM). Compared to PMs, EMs/IMs had significantly more dose adjustments (6.1 vs. 8.1, p = .015). Overall, 33.82% of trough measurements resulted in a dose change. There was no difference in the number of tacrolimus trough measurements between PMs and EM/IMs. The total daily tacrolimus dose requirements were higher in EMs and IMs compared to PMs (<.001). TTR was ∼50% in the PMs and EMs/IMs groups. CYP3A5 EM/IM metabolizers have more tacrolimus dose changes and higher dose requirements which increases clinical management complexity. Larger studies are needed to assess the cost and benefits of including genotyping data to improve clinical management.
Clinicopathological features of atypical glandular cells, not otherwise specified, on cervicovaginal pap smears
Authors: Aytekin Okan , Cakir Caner , Unsal Mehmet , Celik Fatih , Tokalioglu Abdurrahman Alp , Kilic Fatih , Ersak Burak , Codal Bahadır , Kahraman Alper , Gokkaya Mustafa , Ayhan Sevgi , Akar Serra , Cesur Nesibe , Erdogan Fazli , Ozdal Bulent , Oktar Okan , Koc Sevgi , Boran Nurettin , Comert Gunsu Kimyon , Ureyen Isin , Toptas Tayfun , Korkmaz Vakkas , Ustun Yaprak , Tekin Ozlem Moraloglu , Turkmen Osman , Turan Taner
Published: December 2022

Objective

The Papanicolaou (Pap) smear test is a standard screening test that detects cervical lesions and cancers. In this multicentric study, we performed a retrospective analysis of cytological results associated with atypical glandular cells, not otherwise specified (AGC‐NOS).

Methods

We retrospectively reviewed Pap smear tests that resulted as AGC‐NOS. A total of 254 women who underwent colposcopy due to a Pap smear result of AGC‐NOS were included the study between 2003 and 2021. The ages, Pap smear results, HPV results if any, colposcopic biopsy results, endocervical and endometrial pathology results, and management of these patients were analysed.

Results

Two hundred fifty‐four patients with AGC‐NOS Pap smear results were included in the study. A total of 70 (27.6%) patients had cervical and endometrial premalignant or malignant lesions. Malignancy was observed in 17 (6.7%) patients (endometrium, n = 11 [4.3%]; cervix, n = 6 [2.4%]). Isolated premalignant or malignant lesions of the cervix and endometrium were detected in 57 (22.4%) and 12 (4.7%) patients, respectively.

Conclusions

Patients diagnosed with AGC‐NOS should undergo a careful evaluation with all clinicopathological features. Because cancer of the cervix and endometrium is not rare in patients diagnosed with AGC‐NOS, colposcopic examination with endocervical sampling should be a priority based on a cervicovaginal smear. Endometrial sampling is also required according to the patient's clinic, age, and examination characteristics.
Efficacy and tolerability of 1 L polyethylene glycol plus ascorbic acid with senna versus 2 L polyethylene glycol plus ascorbic acid for colonoscopic bowel preparation: Prospective, randomized, investigator‐blinded trial
Authors: Maeda Natsumi , Higashimori Akira , Nakatani Masami , Jinnai Kagami , Kin Daiyu , Sugita Naoko , Morimoto Kenichi , Sasaki Eiji , Fukuda Takashi , Fujiwara Yasuhiro
Published: December 2022

Objectives

Low‐volume polyethylene glycol plus ascorbic acid (PEG‐Asc) reduces the dosage of colonoscopic bowel preparation (BP) solution, but is still poorly tolerated. Adding laxatives to the BP solution reduces the volume of fluid required, without affecting quality. This study aimed to compare 1 L PEG‐Asc plus 24 mg senna (1L‐PEG/AS) and conventional 2 L PEG‐Asc (2L‐PEG/A) regimens on BP quality and patient tolerability.

Methods

A single‐center, randomized, investigator‐blinded, noninferiority trial was performed between June and August 2022. Outpatients scheduled for colonoscopy were randomized (1:1) to the 1L‐PEG/AS or 2L‐PEG/A group. The Boston Bowel Preparation Scale (BBPS) was used to evaluate BP quality. Adverse events and tolerability were surveyed using questionnaires.

Results

Overall, 344 patients received 1L‐PEG/AS or 2L‐PEG/A regimens. The baseline characteristics and adverse events of the two groups were comparable. The 1L‐PEG/AS group showed noninferior adequate BP rates compared with the 2L‐PEG/A group (88% vs. 89%, P = 1.00); overall BBPS was 7.1 ± 1.5 and 7.2 ± 1.5, respectively (P = 0.39). Higher willingness to repeat the BP was observed in the 1L‐PEG/AS group (85% vs. 62%, P < 0.01).

Conclusions

The 1L‐PEG/AS regimen was comparable to the 2L‐PEG/A regimen in terms of BP adequacy, requiring lower BP solution volumes, with better patient tolerance. Thus, it may be a suitable alternative to the conventional BP solution for colonoscopy.

The Japan Registry of Clinical Trials (jRCT1051220043).
Development and validation of a prediction model for histologic progression in patients with nondysplastic Barrett's esophagus
Authors: Peleg Noam , Ringel Yehuda , Shamah Steven , Schmilovitz‐Weiss Hemda , Leshno Moshe , Benjaminov Fabiana , Shinhar Nadav , Gingold‐Belfer Rachel , Dotan Iris , Sapoznikov Boris
Published: December 2022

Objectives

Patients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE).

Methods

A longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low‐grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end‐point was histopathologic progression to LGD, high‐grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation.

Results

A total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long‐segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow‐up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil‐to‐lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77–2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09–1.36, P < 0.001), age (OR 1.03, 95% CI 1.02–1.05, P = 0.02), smoking (OR 1.66, 95% CI 1.09–2.75, P = 0.04), and renal failure (OR 1.51, 95% CI 0.93–2.43, P = 0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively.

Conclusion

This novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs.
Risk‐scoring system for predicting challenging cases of peroral endoscopic myotomy
Authors: Nakai Tatsuya , Abe Hirofumi , Tanaka Shinwa , Kawara Fumiaki , Toyonaga Takashi , Sakaguchi Hiroya , Ueda Chise , Ikezawa Nobuaki , Tsuda Kazunori , Urakami Satoshi , Kodama Yuzo
Published: December 2022

Objectives

Peroral endoscopic myotomy (POEM) is an effective treatment for esophageal motility disorders including achalasia and its variants. However, some surgeons have encountered challenging cases. This study aimed to develop a risk‐scoring system to predict challenging cases of POEM.

Methods

Consecutive patients who underwent POEM between April 2015 and March 2020 at our hospital were included in this single‐center retrospective study. Challenging cases of POEM were defined as patients with any of the following: (i) procedure time ≥90 min; (ii) mucosal perforation; (iii) pneumothorax; and (iv) major bleeding. A risk‐scoring system for predicting challenging cases was developed based on multivariate logistic regression and internal validation was performed using the bootstrap method. Clinical usefulness was evaluated using a decision curve analysis.

Results

Of the 467 patients, 59 (12.6%) had challenging POEM. A risk‐scoring system consisted of four variables: duration of symptoms ≥5 years (assigned score, 1 point), antithrombotics use (1 point), manometric diagnosis of achalasia variants (2 points), and dilation grade 3 (2 points). Our scoring system showed satisfactory discrimination (area under the receiver operating characteristic curve, 0.69; 95% confidence interval [CI] 0.61–0.77) and calibration (slope, 0.99; 95% CI 0.65–1.35). The decision curve analysis demonstrated its clinical usefulness.

Conclusions

We established a risk‐scoring system to predict challenging cases of POEM. This scoring system may aid the selection of patients who require treatment from experienced surgeons.
Neurobiological predispositions for musicality: White matter in infancy predicts school‐age music aptitude
Authors: Zuk Jennifer , Vanderauwera Jolijn , Turesky Ted , Yu Xi , Gaab Nadine
Published: December 2022

Musical training has long been viewed as a model for experience‐dependent brain plasticity. Reports of musical training‐induced brain plasticity are largely based on cross‐sectional studies comparing musicians to non‐musicians, which cannot address whether musical training itself is sufficient to induce these neurobiological changes or whether pre‐existing neuroarchitecture before training predisposes children to succeed in music. Here, in a longitudinal investigation of children from infancy to school age (n = 25), we find brain structure in infancy that predicts subsequent music aptitude skills at school‐age. Building on prior evidence implicating white matter organization of the corticospinal tract as a neural predisposition for musical training in adults, here we find that structural organization of the right corticospinal tract in infancy is associated with school‐age tonal and rhythmic musical aptitude skills. Moreover, within the corpus callosum, an inter‐hemispheric white matter pathway traditionally linked with musical training, we find that structural organization of this pathway in infancy is associated with subsequent tonal music aptitude. Our findings suggest predispositions prior to the onset of musical training from as early as infancy may serve as a scaffold upon which ongoing musical experience can build.

Research Highlights

Structural organization of the right corticospinal tract in infancy is associated with school‐age musical aptitude skills.

Longitudinal associations between the right corticospinal tract in infancy and school‐age rhythmic music aptitude skills remain significant even when controlling for language ability.

Findings support the notion of predispositions for success in music, and suggest that musical predispositions likely build upon a neural structural scaffold established in infancy.

Findings support the working hypothesis that a dynamic interaction between predisposition and experience established in infancy shape the trajectory of long‐term musical development.
The road to normalization: The importance of the United Arab Emirates' neoliberal foreign policy in the normalization with Israel: 2004–2020
Authors: Traub Daniela , Cohen Ronen A. , Kertcher Chen
Published: December 2022

The article discusses the question of why and how the normalization between the United Arab Emirates (UAE) and Israel took place and managed to evolve into a peace agreement. It offers an additional explanation to the neorealists' scholarly and commonly accepted argument: that it was only the behavior of the revisionist state of Iran that was the motive for signing the peace agreement between the two states. Furthermore, the article argues that the normalization of relations began in 2004 and could have materialized owing to the UAE's neoliberal foreign policy of focusing on soft power cooperation. It suggests the UAE's internal interests of status, stability, and empowerment, which were incorporated in the Vision 2021 plan, were translated into a foreign policy of international cooperation rather than one of military involvement and alliances. The UAE's long‐term strategy reveals a dual neorealist and neoliberal foreign policy with a tendency toward the latter. The neoliberal foreign policy of soft power cooperation attracted the UAE to Israel and, through these shared interests, built trust and eventually led to normalization between the two states. The study covers three periods of the UAE's foreign policy strategy during the development of the normalization process. It begins with the tension between the neoliberal and neorealist strategies from 2004 to 2009, then looks at the increase in tensions between 2010 and 2018, and ends with the focus on the neoliberal foreign policy strategy in 2019–2020.
The influence of government upon multinational company manufacturing location decisions
Authors: Ekhart Gerard , Breese Richard
Published: December 2022

With the rapid changes taking place in international manufacturing, there is a need for new theories linking the drivers for manufacturing location decisions to the influence of government. A Delphi study in 2017 of senior industrialists in Europe from capital intensive, complex technology manufacturing sectors provided evidence on the importance of government‐specific factors for final location decisions. This was because of the influence of government policies as an exogenous factor on the drivers for international manufacturing, including cost effective, flexible supply chains and the use of the new technologies of Industry 4.0, in an uncertain global political climate. The findings are used to develop a new theoretical framework comprising the decision onion and the government policy matrix for multinational company manufacturing location decisions. This systematic approach to the influence of government will assist in the development of policy in the post‐Covid 19 era of transformational change in industrial location strategies.
Demoralizing care: Moral and ethical dilemmas of parenting a young adult who lives with a borderline diagnosis
Authors: O'Dougherty Maureen
Published: December 2022

This article theorizes chronic crises of care parents face concerning how to morally/ethically support their young adult child diagnosed with borderline personality disorder (BPD). Grounded in five years’ attendance at a support group for families living with BPD and interviews with parents, the article asks: In the era of deinstitutionalization of those with mental illness, what are the moral/ethical dimensions of parents’ experiences caring for their young adult? The concept of demoralization and “moral breakdown,” an ethical crisis demanding a resolution, characterizes parents’ experiences. The parents featured convey anguished struggles over what they ought to do in a context where risks are high, and nothing parents do seems right. I suggest that dwelling indefinitely in demoralizing care is untenable and that a state of demoralization emerges as a testimony to the parents’ inability to identify a morally/ethically acceptable resolution to the crises of care.
Effects of hunting on genetic diversity, inbreeding and dispersal in Finnish black grouse (Lyrurus tetrix)
Authors: Chen Rebecca S. , Soulsbury Carl D. , Lebigre Christophe , Ludwig Gilbert , van Oers Kees , Hoffman Joseph I.
Published: December 2022

Intensive hunting activities such as commercial fishing and trophy hunting can have profound influences on natural populations. However, less intensive recreational hunting can also have subtle effects on animal behaviour, habitat use and movement, with implications for population persistence. Lekking species such as the black grouse (Lyrurus tetrix) may be especially prone to hunting as leks are temporally and spatially predictable, making them easy targets. Furthermore, inbreeding in black grouse is mainly avoided through female‐biased dispersal, so any disruptions to dispersal caused by hunting could lead to changes in gene flow, increasing the risk of inbreeding. We therefore investigated the impact of hunting on genetic diversity, inbreeding and dispersal on a metapopulation of black grouse in Central Finland. We genotyped 1065 adult males and 813 adult females from twelve lekking sites (six hunted, six unhunted) and 200 unrelated chicks from seven sites (two hunted, five unhunted) at up to thirteen microsatellite loci. Our initial confirmatory analysis of sex‐specific fine‐scale population structure revealed little genetic structure in the metapopulation. Levels of inbreeding did not differ significantly between hunted and unhunted sites in neither adults nor chicks. However, immigration rates into hunted sites were significantly higher among adults compared to immigration into unhunted sites. We conclude that the influx of migrants into hunted sites may compensate for the loss of harvested individuals, thereby increasing gene flow and mitigating inbreeding. Given the absence of any obvious barriers to gene flow in Central Finland, a spatially heterogeneous matrix of hunted and unhunted regions may be crucial to ensure sustainable harvests into the future.
A decade of progress in marine evolutionary biology
Authors: De Wit Pierre , Faust Ellika , Green Leon , Jahnke Marlene , Pereyra Ricardo T. , Rafajlović Marina
Published: December 2022

This article summarizes the Evolutionary Applications Special Issue, “A decade of progress in Marine Evolutionary Biology.” The globally connected ocean, from its pelagic depths to its highly varied coastlines, inspired Charles Darwin to develop the theory of evolution during the voyage of the Beagle. As technology has developed, there has been a dramatic increase in our knowledge about life on our blue planet. This Special Issue, composed of 19 original papers and seven reviews, represents a small contribution to the larger picture of recent research in evolutionary biology, and how such advancements come about through the connection of researchers, their fields, and their knowledge. The first European network for marine evolutionary biology, the Linnaeus Centre for Marine Evolutionary Biology (CeMEB), was developed to study evolutionary processes in the marine environment under global change. Though hosted by the University of Gothenburg in Sweden, the network quickly grew to encompass researchers throughout Europe and beyond. Today, more than a decade after its foundation, CeMEB's focus on the evolutionary consequences of global change is more relevant than ever, and knowledge gained from marine evolution research is urgently needed in management and conservation. This Special Issue, organized and developed through the CeMEB network, contains contributions from all over the world and provides a snapshot of the current state of the field, thus forming an important basis for future research directions.
Encountering Berlant part two: Cruel and other optimisms
Authors: Anderson Ben , Awal Akanksha , Cockayne Daniel , Greenhough Beth , Linz Jess , Mazumdar Anurag , Nassar Aya , Pettit Harry , Roe Emma J. , Ruez Derek , Salas Landa Mónica , Secor Anna , Williams Aelwyn
Published: December 2022

Part 2 of Encountering Berlant amplifies the promise of Lauren Berlant's influential concept of ‘cruel optimism’. Cruel optimism names a double‐bind in which attachment to an ‘object’ holds out the promise of sustaining/flourishing, whilst simultaneously harming. The lines between harming, sustaining, damaging and flourishing blur, sometimes collapsing entirely. By holding together opposites the concept exemplifies and performs the centrality of ambivalence to Berlant's thought, as well as their orientation to overdetermination and incoherence. Geographers and others have found in the concept a way of understanding the intersection between affective and political economies in the crisis‐present following the 2008 financial crisis. Together with Berlant's linked concepts such as ‘crisis ordinariness’ and ‘impasse’, cruel optimism has offered a way of understanding why detachment can be so difficult and how damaging conditions endure. Contributors begin from these starting points, amplifying the concept's promise: a new way of researching and writing about the reproduction of ordinary damage and harm. By writing from diverse encounters with Berlant's work, they move the concept in multiple directions, juxtaposing it with other optimisms across a variety of empirical scenes and locations. The result is a repository of what cruel optimism, and Berlant's mode of thinking‐feeling more broadly, offer geographers and others.
Money down the drain: Corruption and water service quality in Africa
Authors: Breen Michael , Gillanders Robert
Published: December 2022

Using data from the seventh round of the Afrobarometer, we find that a greater regional incidence of corruption in the utilities sector is associated with a reduced likelihood that a household reports that it has access to enough clean water. This result is not evident in older rounds of the survey that were conducted prior to methodological improvements made in round seven. Moreover, this association holds only in areas with a piped water system. Thus, our findings are consistent with the argument that corruption is a barrier to accessing water through its impact on the quality of water services. While a household that has paid a bribe is more likely to have a water access point, the regional incidence of utilities corruption predicts that the household will not have enough clean water. Individual acts of bribery, while associated with connection to a water network, are not associated with greater access in reality.
The influence of the COVID‐19 pandemic on changes in perceived work pressure for Dutch mothers and fathers
Authors: André Stéfanie , van der Zwan Roos
Published: December 2022

As a result of the first COVID‐19 lockdown in the Netherlands in March 2020, more than half of parents in the Netherlands had to work from home while also caring for their children. We found that work‐related stressors and resources (working more hours, realistic manager expectations) particularly affect perceived work pressure. Perceived work pressure was higher among egalitarian fathers and mothers, especially compared to traditional fathers and mothers. Furthermore, egalitarian fathers were more negatively affected by arguments with their partners (home stressor) than traditional fathers. We found no differences between traditional and egalitarian mothers.
Primary prophylaxis in children with severe haemophilia A and B—Implementation over the last 20 years as illustrated in real‐world data in the PedNet cohorts
Authors: Ljung Rolf , de Kovel Marloes , van den Berg H. Marijke ,   the PedNet study group
Published: December 2022

Introduction

The prophylactic regimen in children with severe haemophilia is suggested in various publications and guidelines. Few data exist on its implementation in clinical practice.

Aim

To investigate the implementation of primary prophylaxis based on real‐life data from PedNet during the last 20 years.

Methods

All children from the PedNet cohort (n = 1260) with severe haemophilia A (SHA) or severe haemophilia B (SHB), FVIII/IX < .01 IU/mL, born between 2000 and 2009 (Cohort I; SHA n = 662; SHB n = 88) and 2010–2019 (Cohort II; SHA n = 598; SHB n = 94) were included.

Results

In SHA, the median age at start of prophylaxis was 17.3 months (IQR; 12.5–26.1) in Cohort I which decreased to 13.1 months (IQR; 10.4–19.1) in Cohort II (p < .000). “Once‐a‐week” prophylaxis at start increased from 49% to 68% (SHA) and 38% to 70% (SHB). FVIII doses were reduced from median 43.5 (IQR; 34.6–49.0) to 30.9 IU/kg (IQR; 26.3–46.3), while dosing with FIX did not change. After 2010 approximately 60% of the patients with SHA and SHB started prophylaxis before any joint bleed. The number of CVADs needed in both cohorts was around 30%. Incidences of inhibitors were unchanged: SHA (∼31%) and SHB (∼10%). Sporadic cases were diagnosed significantly later (median 8.3 months; IQR; 3.7–11.9) and they had more joint bleeds before start of prophylaxis.

Conclusion

Primary prophylaxis nowadays starts at an earlier age: before any joint bleed (60% of patients with SHA and SHB). Approximately 70% started on a once‐weekly schedule with significantly reduced doses in SHA but unchanged in SHB.
Molecular spectrum of inherited FVII deficiency in North India revealed a recurrent variant with a founder effect
Authors: Sharma Ritika , Jamwal Manu , Senee Hari Kishan , Singh Namrata , Kumar Narender , Hans Chander , Kler Anita , Bansal Deepak , Trehan Amita , Malhotra Pankaj , Ahluwalia Jasmina , Das Reena
Published: December 2022

Introduction

Inherited Factor VII (FVII) deficiency is commonest among the rare bleeding disorders. A small number of patients present in infancy with severe bleeding, and many may remain asymptomatic but detected before surgery/invasive procedures. Genetic testing may be helpful in predictive testing/prenatal diagnosis in severe cases.

Aim

Characterisation of clinical and genotypic spectrum of patients with inherited FVII deficiency.

Methods

Retro‐prospectively, 35 cases with prolonged prothrombin time and FVII activity (FVII:C) <50 IU/dl were subjected to targeted resequencing. After in‐silico analysis, variant/s were validated by Sanger sequencing in index cases and family members. Haplotype analysis was done for F7 polymorphisms.

Results

Severe FVII deficiency was found in 50% of patients (FVII:C ≤1 IU/dl), and 42.9% were asymptomatic. Clinical severity assessment revealed 17% severe, 17% moderate and 22.9% patients with mild bleeds. FVII levels ranged from .3 to 38 IU/dl. Molecular analysis revealed variants in 30/35 cases, of which 17 were homozygous, 10 were compound heterozygous and 3 were heterozygous. Twelve genetic variants were identified, one promoter variant c.‐30A>C; seven missense (c.215C>G, c.244T>C, c.253G>C, c.904G>A, c.961C>T, c.1109G>T, c.1211G>A), two deletions (c.21delG, c.868_870delATC), and one each of nonsense c.634C>T and splice‐site variant c.316+1G>A. Recurrent variants c.1109G>T and c.215C>G were found in 17 and 8 cases, 12 of the former cases were homozygous. They had the same haplotype, indicating the founder effect in North Indians.

Conclusion

This is the largest cohort of FVII genotyping from India, confirming heterogeneity in terms of clinical manifestations, FVII activity and zygosity of the variants with a limited genotypic phenotypic correlation.
Comparison of microscopy and metabarcoding to identify pollen used by the critically endangered rusty patched bumble bee, Bombus affinis
Authors: Simanonok Michael P. , Iwanowicz Deborah D. , Raines Clayton D. , Wood Thomas J. , Isaacs Rufus , Cornman Robert S. , Otto Clint R. V.
Published: December 2022

Taxonomic analysis of pollen collected by bees can provide insights into their host plant use, providing information about the plant species selected for targeted conservation strategies. The two main identification approaches used are morphological analysis of pollen samples affixed to microscope slides (i.e., microscopic palynology) and molecular analysis of samples. Both methods are widely used for freshly collected materials and have been compared in multiple studies, yet their application to archived samples remains to be explored. Archived samples may be particularly useful for the study of rare or protected species, particularly when historical foraging patterns are uncertain.

We used both methods to analyse pollen collected by the endangered rusty patched bumble bee species, Bombus affinis Cresson, applied to museum‐archived specimens. Pollen samples were removed from the corbiculae of bumble bees originally collected in Michigan between 1914 and 1974. Samples included 24 rusty patched bumble bees each with large pollen loads on both corbiculae, allowing for pollen from the same bee to be analysed using both methods.

DNA metabarcoding detected more plant taxa than light microscopy, and DNA barcoding also had higher taxonomic resolution when compared to taxa determined using light microscopy. In many instances, pollen could only be confidently identified to tribe or family with light microscopy. Discrepancy between methods decreased when taxa identified via DNA metabarcoding were binned into ecologically relevant groups corresponding to those identified using light microscopy.

Although binning demonstrated smaller within‐method variance, there was still minimal correspondence between the two methods. Results indicate there are benefits and biases unique to each method and highlight the utility of binning taxonomic results to morphological or ecological groupings.
A C2H2 zinc finger transcription factor of the whitefly Bemisia tabaci interacts with the capsid proteins of begomoviruses and inhibits virus retention
Authors: Ghosh Saptarshi , Srinivasan Rajagopalbabu , Ghanim Murad
Published: December 2022

Begomoviruses are a group of ssDNA viruses exclusively transmitted by the whitefly Bemisia tabaci and constrain vegetable production in the old and new worlds. Although multiple molecular determinants governing the transmission of begomoviruses by whiteflies have been unravelled, factors critical for transmission majorly remain unknown. In this study, a whitefly C2H2 zinc finger (ZF) protein, 100% identical to the vascular endothelial ZF‐like gene (vezf) protein was confirmed to interact with the CP of both old‐ and new‐world begomoviruses. This was achieved by a yeast two‐hybrid (Y2H) system screening of a whitefly cDNA library using capsid protein (CP) of TYLCV as a bait. In silico annotation of vezf protein revealed that it contains a N‐terminal ZF‐associated domain (ZAD) alongside multiple C2H2 ZF domains on the C‐terminal end. ZAD‐ZF proteins form the most abundant class of transcription factors within insects. Herein, we validated the interaction of vezf with four diverse begomoviruses and its functional role in begomovirus transmission. Silencing of the vezf gene of B. tabaci led to increased retention of three diverse begomoviruses tested. Vezf is the first insect transcription factor identified to interact with plant viruses and can be crucial to understand the possible mechanisms by which plant viruses modulate transcription of their insect vectors during transmission.
FLU‐LISA (fluorescence‐linked immunosorbent assay): high‐throughput antibody profiling using antigen microarrays
Authors: Levy Shlomia , Abd Alhadi Marwa , Azulay Asaf , Kahana Amit , Bujanover Nir , Gazit Roi , McGargill Maureen A , Friedman Lilach M , Hertz Tomer
Published: December 2022

Vaccination and natural infection both elicit potent humoral responses that provide protection from subsequent infections. The immune history of an individual following such exposures is in part encoded by antibodies. While there are multiple immunoassays for measuring antibody responses, the majority of these methods measure responses to a single antigen. A commonly used method for measuring antibody responses is ELISA—a semiquantitative assay that is simple to perform in research and clinical settings. Here, we present FLU‐LISA (fluorescence‐linked immunosorbent assay)—a novel antigen microarray‐based assay for rapid high‐throughput antibody profiling. The assay can be used for profiling immunoglobulin (Ig) G, IgA and IgM responses to multiple antigens simultaneously, requiring minimal amounts of sample and antigens. Using several influenza and severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) antigen microarrays, we demonstrated the specificity and sensitivity of our novel assay and compared it with the traditional ELISA, using samples from mice, chickens and humans. We also showed that our assay can be readily used with dried blood spots, which can be collected from humans and wild birds. FLU‐LISA can be readily used to profile hundreds of samples against dozens of antigens in a single day, and therefore offers an attractive alternative to the traditional ELISA.
Understanding the contribution of general medical services to acute inpatient care in Victorian public hospitals
Authors: Gorman Andrew Christopher , Newnham Harvey H. , Potter Elizabeth L. , Busija Lucy , Aung Ar Kar
Published: December 2022

Background

General medicine is an integral part of health services, yet there is little data highlighting their contribution to acute hospital care in Australia.

Aims

To utilise the Victorian Department of Health's administrative dataset for hospital admissions to evaluate the relative contribution and trends over time of general medical services to acute multiday inpatient hospital separations in the Victorian public healthcare system.

Methods

A retrospective time‐series study of general medical activity compared to other major specialties using hospital‐level data provided by the Department of Health: (i) extrapolation from diagnosis‐related group (DRG) activity data (2011–2021) and, (ii) directly reported discharge unit‐based activity (available from 2018). Acute multiday separations of all patients aged ≥18 years from all metropolitan and rural Victorian public hospitals were included.

Results

Using the DRG‐based data, general medicine ranked as the largest care provider of all specialties studied, accounting for 12.1% of separations. Despite the largest increase at a rate of 2831 separations/year (0.336%/year of total, P < 0.001) compared to others, mean length of stay declined by 0.08 days/year (P < 0.001). These findings were significant for metropolitan and rural hospitals. The use of directly reported discharge unit‐based data also ranked general medicine as the largest care provider accounting for 32.9% of total separations, with rural hospital general medical services contributing nearly 50% of all multiday separations.

Conclusions

Both DRG‐based data and discharge unit‐based data indicate that general medicine is the largest provider of acute multiday inpatient care in Victorian hospitals. The estimate of contribution of general medicine differed between the two datasets as DRG data likely over‐represents the role of other specialties possibly due to assumptions regarding specialty management of varying groups of diagnoses.
The role of HMGB1 in COVID‐19‐induced cytokine storm and its potential therapeutic targets: A review
Authors: Wulandari Sri , Hartono  , Wibawa Tri
Published: December 2022

Hyperinflammation characterized by elevated proinflammatory cytokines known as ‘cytokine storms’ is the major cause of high severity and mortality seen in COVID‐19 patients. The pathology behind the cytokine storms is currently unknown. Increased HMGB1 levels in serum/plasma of COVID‐19 patients were reported by many studies, which positively correlated with the level of proinflammatory cytokines. Dead cells following SARS‐CoV‐2 infection might release a large amount of HMGB1 and RNA of SARS‐CoV‐2 into extracellular space. HMGB1 is a well‐known inflammatory mediator. Additionally, extracellular HMGB1 might interact with SARS‐CoV‐2 RNA because of its high capability to bind with a wide variety of molecules including nucleic acids and could trigger massive proinflammatory immune responses. This review aimed to critically explore the many possible pathways by which HMGB1‐SARS‐CoV‐2 RNA complexes mediate proinflammatory responses in COVID‐19. The contribution of these pathways to impair host immune responses against SARS‐CoV‐2 infection leading to a cytokine storm was also evaluated. Moreover, since blocking the HMGB1‐SARS‐CoV‐2 RNA interaction might have therapeutic value, some of the HMGB1 antagonists have been reviewed. The HMGB1‐ SARS‐CoV‐2 RNA complexes might trigger endocytosis via RAGE which is linked to lysosomal rupture, PRRs activation, and pyroptotic death. High levels of the proinflammatory cytokines produced might suppress many immune cells leading to uncontrolled viral infection and cell damage with more HMGB1 released. Altogether these mechanisms might initiate a proinflammatory cycle leading to a cytokine storm. HMGB1 antagonists could be considered to give benefit in alleviating cytokine storms and serve as a potential candidate for COVID‐19 therapy.
The road to conventional tool use: Developmental changes in children's material engagement with artifacts in nursery school
Authors: Alessandroni Nicolás
Published: December 2022

The development of tool use in early childhood is a topic of continuing interest in developmental psychology. However, the lack of studies in ecological settings results in many unknowns about how children come to use artifacts according to their cultural function. We report a longitudinal study with 17 sociodemographically diverse children (8 female) attending a nursery school in Madrid (Spain) and their two adult female teachers. Using mixed‐effects models and Granger causality analysis, we measured changes in the frequency and duration of children's object uses between 7 and 17 months of age and in the directional influences among pairs of behaviors performed by teachers and children. Results show a clear shift in how children use artifacts. As early as 12 months of age, the frequency of conventional uses outweighs that of all other types of object use. In addition, object uses become shorter in duration with age, irrespective of their type. Moreover, certain teachers' nonlinguistic communicative strategies (e.g., demonstrations of canonical use and placing gestures) significantly influence and promote children's conventional tool use. Findings shed light on how children become increasingly proficient in conventional tool use through interactions with artifacts and others in nursery school.
Are we there yet? A guide to achieving endemic status for COVID‐19 and variants
Authors: McDonald Tracey
Published: December 2022

Aim

To clarify factors that support a policy change from pandemic to endemic status and to examine options for non‐medical responses to reduce COVID‐19 transmission.

Background

Critical factors to be considered in pandemic response decisions are not limited to medical options or public health orders, although these are important.

Sources of evidence

All evidence drawn from publicly available sources is presented through the lens of the authors’ nursing, management, education, policy and research experience.

Discussion

As COVID‐19 variants cause infections to surge nurses and other health practitioners, who are the de facto implementers of public and health policy, need to consider the evidence supporting a pandemic policy change to endemic status. Non‐medical options for reducing transmission and variant mutations are needed to enable at‐risk populations to avoid infection.

Conclusion

Public policy that shifts infection risks onto the general population requires close scrutiny of the evidence base for such decisions and warrants open debate and review. If people are to manage risks arising from policy decisions, they need access to non‐medical virus detection options as well as access to effective medicines and treatment.

Implications for nursing practice

Nurses have an extension to their advocacy role when policy changes about infectious disease status are declared. Evaluation of policy in terms of validity, equity and scientific basis is part of nursing's public responsibility. Policies that fail to reflect what is happening at the patient care level need to be questioned and modified where necessary. Only policies deemed ‘good’ policy by nurses should be implemented without challenge. Access to devices for environmental detection of the virus would enable real‐time estimation of infection risks and inform individual decisions about the real risk of participating in work or other activities.

Implications for health and social policy

Policy decisions to transition from pandemic to endemic status must be evidence based. Clear messaging about risks and options assists policy implementation. Terminologies describing stages of infectious disease spread from ‘outbreak, epidemic, endemic and pandemic’ are not interchangeable, although they will expand and contract across the range in response to interventions such as public health safety measures (PHSM), quarantine, vaccinations, antivirals and fatalities that alter the case count in defined locations for those who avoid or survive an infection.
Initial experience with stylet‐driven versus lumenless lead delivery systems for left bundle branch area pacing
Authors: Braunstein Eric D. , Kagan Ruth D. , Olshan David S. , Gabriels James K. , Thomas George , Ip James E. , Markowitz Steven M. , Lerman Bruce B. , Liu Christopher F. , Cheung Jim W.
Published: December 2022

Introduction

Left bundle branch area pacing (LBBP) has emerged as an alternative method for conduction system pacing. While initial experience with delivery systems for stylet‐driven and lumenless lead implantation for LBBP has been described, data comparing outcomes of stylet‐driven versus lumenless lead implantation for LBBP are limited. In this study, we compare success rates and outcomes of LBBP with stylet‐driven versus lumenless lead delivery systems.

Methods

Eighty‐three consecutive patients (mean age 74.1 ± 11.2 years; 56 [68%] male) undergoing attempted LBBP at a single institution were identified. Cases were grouped by lead delivery systems used: stylet‐driven (n = 53) or lumenless (n = 30). Baseline characteristics and procedural findings were recorded and compared between the cohorts. Intermediate term follow‐up data on ventricular lead parameters were also compared.

Results

Baseline characteristics were similar between groups. Successful LBBP was achieved in 77% of patients, with similar success rates between groups (76% in stylet‐driven, 80% in lumenless, p = 0.79), and rates of adjudicated LBB capture and other paced QRS parameters were also similar. Compared with the lumenless group, the stylet‐driven group had significantly shorter procedure times (90 ± 4 vs. 112 ± 31 min, p = 0.004) and fluoroscopy times (10 ± 5 vs. 15 ± 6 min, p = 0.003). Ventricular lead parameters at follow‐up were similar, and rates of procedural complications and need for lead revision were low in both groups.

Conclusion

Delivery systems for stylet‐driven and for lumenless leads for LBBP have comparable acute success rates. Long‐term follow‐up of lead performance following use of the various delivery systems is warranted.
Left atrial epicardial adipose tissue exacerbates electrical conduction disturbance in normal‐weight patients undergoing pulmonary vein isolation for atrial fibrillation
Authors: Yamada Shinya , Kaneshiro Takashi , Nodera Minoru , Amami Kazuaki , Nehashi Takeshi , Takeishi Yasuchika
Published: December 2022

Introduction

Epicardial adipose tissue (EAT) exacerbates both electrical and structural remodeling in obese atrial fibrillation (AF) patients, but the impacts of EAT on atrial arrhythmogenicity remain unclear in normal‐weight AF patients. Therefore, we sought to investigate this issue using electroanatomic mapping.

Methods and Results

We enrolled drug‐refractory 105 paroxysmal AF patients in the normal body mass index range (18.5–24.9 kg/m2), who had undergone electroanatomic mapping after pulmonary vein isolation (PVI). One day before PVI, we assessed P‐wave duration in a 12‐lead electrocardiogram and left atrial (LA)‐EAT volumes using contrast‐enhanced computed tomography. The patients were divided into two groups based on the median LA‐EAT volume (16.0 ml); the high LA‐EAT group (≥16.0 ml, n = 53) and low LA‐EAT group (<16.0 ml, n = 52). We compared P‐wave duration, LA conduction velocity and bipolar voltage, the presence of low‐voltage zone (<0.5 mV), and LA volume index on echocardiography between the two groups. The LA bipolar voltage, low‐voltage zone, and LA volume index were not different between the high and low LA‐EAT groups. However, P‐wave duration was significantly longer in the high group than in the low group (p < .001). Additionally, the LA conduction velocity was significantly more depressed in the high group than in the low group (p < .001). Multivariate linear regression analysis revealed that LA‐EAT volume was correlated with P‐wave duration (β = .367, p < .001) and conduction velocity (β = −.566, p < .001), respectively.

Conclusions

Increased LA‐EAT volumes were associated with electrical conduction disturbance after PVI in normal‐weight patients with AF. P‐wave duration may be a clinically useful predictor of LA‐EAT.
Parental suicide attempts and offspring mental health problems in childhood and adolescence
Authors: Ortin‐Peralta Ana , Kerkelä Martta , Veijola Juha , Gissler Mika , Sourander Andre , Duarte Cristiane S.
Published: December 2022

Background

The relationship between parental suicide attempts and offspring suicide risk has been established. However, the impact of parental suicide attempts on mental health problems in offspring as youth remains unexplored. This study examined the prospective association between parental suicide attempts and offspring internalizing, externalizing, and attention/hyperactivity problems in childhood and adolescence. We also examined how offspring mental health problems in childhood mediated the association between parental suicide attempts and offspring mental health problems in adolescence.

Methods

A subsample of 6,381 (48.4% female) cohort members with complete data on mental health problems in childhood and adolescence was extracted from the Northern Finland Birth Cohort 1986 Study. Offspring mental health problems were assessed via teacher's Rutter B2 scale during the childhood assessment (child's age of 8) and the Youth Self‐Report scale (child's age of 15/16). Information about first parental suicide attempts was collected using ICD codes from hospital discharge records.

Results

Lifetime parental suicide attempts during the study period (N = 95) were associated with offspring internalizing, externalizing, and attention/hyperactivity problems in adolescence. Parental suicide attempts before the childhood assessment (N = 55) were associated with offspring behavioral problems in childhood [B (95% CI) = .64 (0.08–1.28)]. In the mediation models, parental suicide attempts before the childhood assessment had a significant indirect effect on offspring externalizing [B (95% CI) = .03 (0.01–0.05)] and attention/hyperactivity problems [B (95% CI) = .02 (0.01–0.04)] in adolescence via offspring behavioral problems in childhood.

Conclusions

Our findings highlight the importance of assessing and monitoring mental health problems in offspring whose parents have been hospitalized for attempting suicide. Among children with behavioral problems, clinicians should inquire about parental history of suicide attempts, as children with familial vulnerability to suicide may develop externalizing and attention/hyperactivity problems in adolescence.