bluuebunny/crossref_metadata_2025_split huggingface dataset:
Humoral and cellular immune responses and their kinetics vary in dependence of diagnosis and treatment in immunocompromised patients upon COVID-19 mRNA vaccination
Authors: Wagner A. , Garner-Spitzer E. , Schötta A. , Orola M. , Wessely A. , Zwazl I. , Ohradanova-Repic A. , Tajti G. , Gebetsberger L. , Kratzer B. , Tomosel E. , Kutschera M. , Tobudic S. , Pickl W. F. , Kundi M. , Stockinger H. , Novacek G. , Reinisch W. , Zielinski C , Wiedermann U. 
Published: December 2021

AbstractBackgroundKnowledge about humoral and cellular immunogenicity and their kinetics following SARS-CoV-2 mRNA vaccinations in immunosuppressed patients is limited.MethodsAntibody and cytokine responses were assessed in 263 patients with either solid tumors (SOT, n=63), multiple myeloma (MM, n=70) or inflammatory bowel diseases (IBD, n=130) undergoing various immunosuppressive regimens and from 66 healthy controls before the first and the second, as well as four weeks and 5-6 months after the second mRNA vaccine dose with either BNT162b2 or mRNA-1273.FindingsFour weeks after the second dose, seroconversion was lower in cancer than in IBD patients and controls, with the highest non-responder rate in MM patients (17.1%). S1-specific IgG levels correlated with neutralizing antibody titers. While antibody responses correlated with cellular responses in controls and IBD patients, IFN-γ and antibody responses did not in SOT and MM patients. At six months, 19.6% of patients with MM and 7.3% with SOT had become seronegative, while IBD patients and controls remained seropositive in 96.3% and 100%, respectively. Vaccinees receiving mRNA-1273 presented higher antibody levels than those vaccinated with BNT162b2.InterpretationCancer patients may launch an inadequate seroresponse in the immediate time range following vaccination and up to six months, correlating with vaccine-specific cellular responses. These findings propose antibody testing in immunosuppressed - along with cellular testing - provides guidance for administration of additional vaccine doses, or may indicate the necessity for antibody treatment. IBD patients respond well to the vaccine, but treatment such as with TNF-α inhibitors may reduce persistence of immune responses.FundingThe study was sponsored and financed by the Medical University of Vienna – third party funding by the Institute of Specific Prophylaxis and Tropical Medicine. AOR. and HS acknowledge funding by the Austrian Science Fund (FWF, P 34253-B).
KRAS G12D can be targeted by potent salt-bridge forming inhibitors
Authors: Mao Zhongwei , Xiao Hongying , Shen Panpan , Yang Yu , Xue Jing , Yang Yunyun , Shang Yanguo , Zhang Lilan , Li Xin , Zhang Yuying , Du Yanan , Chen Chun-Chi , Guo Rey-Ting , Zhang Yonghui 
Published: December 2021

AbstractKRAS mutation occurs in nearly 30% of human cancers, yet the most prevalent and oncogenic KRAS mutation (G12D) still lacks inhibitors. Herein, we explored the formation of a salt-bridge between KRAS’s Asp12 residue and a series of potent inhibitors. Our ITC results show that these inhibitors bind to and inhibit both GDP-bound and GTP-bound KRAS G12D, and our crystallographic studies revealed the structural basis of inhibitor binding in the switch-II pocket, experimentally confirming the formation of a salt-bridge between the piperazine moiety of the inhibitors and the 12D residue of the mutant protein. Among KRAS family proteins and mutants, both ITC and enzymatic assays support the selectivity of the inhibitors for KRAS G12D, and the inhibitors disrupt the KRAS-CRAF interaction. We also observed inhibition of cancer cell proliferation and inhibition of MAPK signaling by a representative inhibitor (TH-Z835); however, since this was not fully dependent on KRAS mutation status, it is possible that our inhibitors may have off-target effects via non-KRAS small GTPases. Experiments with a mouse model of pancreatic cancer showed that TH-Z835 significantly reduced tumor volume and synergized with an anti-PD-1 antibody. Collectively, our study demonstrates proof-of-concept for a salt-bridge, induced-fit pocket strategy for KRAS G12D, which warrants future medicinal chemistry efforts for optimal efficacy and minimized off-target effects.
Mental health correlates of substance use behaviors among a nationally representative sample of juvenile offenders
Authors: Proctor Steven L. , Kopak Albert M. 
Published: December 2021

Purpose
This paper aims to extend previous findings by identifying the mental health correlates of both acute and chronic substance use behaviors among a large nationally representative sample of juvenile offenders.

Design/methodology/approach
Survey of Youth in Residential Placement interview data from 6,920 juvenile offenders (76% male) detained in 290 US facilities were analyzed to determine bivariate relationships between two indicators of substance use (acute and chronic) and seven mental health domains (depression/isolation, anxiety, anger, trauma, inattention, hallucinations and suicidality).

Findings
Prevalence rates of above average indications for all seven mental health domains were significantly higher among offenders under the influence of a substance at the time they committed their instant offense compared to those not under the influence. Offenders with above average indications in the seven studied mental health areas reported a higher level of chronic effects of substance use relative to those with average or below mental health indications.

Practical implications
The results have important implications for the assessment and treatment of co-occurring mental health issues among juvenile offenders with substance use issues. Juveniles with above average mental health indications may be more prone to experiencing a number of substance-related problems. Observed results may guide the implementation of routine assessment procedures at the juvenile detention level. Intake specialists should screen and administer comprehensive mental health assessments for juveniles who report substance intoxication at the time of their instant offense. Juvenile offenders who report clinical levels of mental health symptoms should receive a comprehensive assessment of substance use and related problems.

Originality/value
Although the co-occurrence of substance use and mental health issues among juvenile justice involved populations is well documented, previous research studies in this area have included a number of limitations. Relatively small offender sample populations, often from a single facility, warrant further work with a large, nationally representative sample of juvenile offenders. Inconsistency in measures of substance use and the failure to distinguish between acute and chronic measures of substance use in prior studies also require further investigation. This study contributes to the extant co-occurring substance use and mental health knowledge base by identifying the mental health correlates of both acute and chronic substance use behaviors among a large nationally representative sample of juvenile offenders.
Phenology of Zamia boliviana (Zamiaceae), a threatened species from a seasonally dry biodiversity hotspot in South America
Authors: Segalla Rosane , Pinheiro Fábio , Baronio Gudryan J. , Morellato Leonor Patrícia Cerdeira 
Published: December 2021

AbstractDioecy, a character common to all cycads, requires obligatory outcrossing. The absence of potential reproductive mates of the opposite sex renders individuals effectively sterile. Therefore, reproductive synchrony is essential for the reproductive success of cycads. Here, we describe the reproductive phenology, morphology, and lifespan of strobili of Zamia boliviana (Cycadales, Zamiaceae), an endemic cycad in South America. We examined the variation in timing of maturation between polliniferous and ovuliferous individuals in two Z. boliviana populations. Lifespan of polliniferous and ovuliferous strobili was based on direct observations and systematic measurements of strobili development. Phenological study covered three reproductive cohorts in two distinct cycad populations. Lifespan of polliniferous strobili was comprised of four phases and lasted 50 days until the cycle's completion, while ovuliferous strobili underwent seven phases that extended over 330 days until seed dehiscence. Both sexes produced strobili during the dry season. We identified a seasonally synchronous pattern in the reproductive phenology of Z. boliviana, with a major overlap in the phases of emergence, pollen release, and strobili receptivity between sexes, populations, and subsequent years. Reproductive events of Z. boliviana followed the seasonality of the Cerrado vegetation and climate. Synchrony between the period of strobili production and reproductive activity peaks was found in both sexes, but seed dehiscence occurred in the dry season. Our study provides relevant and new biological data for Z. boliviana in its natural habitat, demonstrating a temporal distinction between the lifespan of polliniferous and ovuliferous strobili and the necessary overlap between the release and receptivity of pollen.
Development of a multiprimer metabarcoding approach to understanding trophic interactions in agroecosystems
Authors: Batuecas Ivan , Alomar Oscar , Castañe Cristina , Piñol Josep , Boyer Stéphane , Gallardo‐Montoya Lorena , Agustí Nuria 
Published: December 2021

AbstractTo understand trophic interactions and the precise ecological role of each predatory species, it is important to know which arthropod and plant resources are used by generalist predators in agroecosystems. Molecular approaches, such as the use of high‐throughput sequencing (HTS), play a key role in identifying these resources. This study develops a multiprimer metabarcoding approach for screening the most common trophic interactions of two predatory arthropods with contrasting morphologies, Rhagonycha fulva (Coleoptera: Cantharidae) and Anthocoris nemoralis (Hemiptera: Anthocoridae) collected from a peach crop. To reduce the time and cost of this metabarcoding approach, we first evaluated the effect of using two different predator‐pools of different size (10 and 23 individuals of the same species). We also used our system to analyze the performance of one and two primer pairs in the same library. Our results show that the analysis of 23 individuals together with the use of two primer pairs in the same library optimize the HTS analysis. Using these best‐performing conditions, we then analyzed the entire bodies of field‐collected predators as well as the washing solutions used to clean the insect bodies. We were able to identify both gut content (i.e., diet) and external pollen load (i.e., on the insects’ bodies). This study also demonstrates the importance of washing predatory insects’ bodies prior to HTS analysis when the target species have a considerable size (>10 mm) and hairy structures. This metabarcoding approach has significant potential for the study of trophic links in agriculture, revealing expected and unexpected trophic relationships.
Geodetic Analysis inside the South Korean Peninsula and Impact of the 2011 Tohoku–Oki (TO) Earthquake
Authors: ANSARI Kutubuddin , PARK Kwan‐Dong 
Published: December 2021

AbstractThe most powerful Tohoku–Oki (TO) earthquake that occurred in Japan on 11 March 2011 affected Japan as well as South Korea. In the current study, we investigated contemporary geodetic deformation inside South Korea before and after the TO earthquake using Global Navigation Satellite System (GNSS) measurements from 01 January 2008 to 31 December 2017. Measured velocities of GNSS sites are modeled by Auto‐regressive moving average (ARMA) method to analyze the long‐term GNSS time‐series variation and to investigate the secular tectonic crustal deformation. We found that the maximum co‐seismic displacements during the TO earthquake reached up to 36.82 ± 0.21 mm in the east and 5.90 ± 0.08 mm in the north directions. The geometric model of the co‐seismic thrust surface was characterized by a rectangular plane with a dip of 12.0° and strike 200°. The thrust is situated at 25 km hypocenter depth, with an area roughly ∼470 km long and ∼120 km wide. The seismicity pattern after the earthquake indicated that the compressional strain started to be replaced by the extensional strain during the post TO earthquake period from 2011 to 2014. Further, the strain became predominantly extensional during the period 2015 to 2017, revealing an effective rotational change that occurred inside the Korean Peninsula.
Miliarial gout: Clinical case and a brief review
Authors: Wei Lei , Wee Charlene Li Ping , Lee Joyce Siong See , Wang Ding Yuan 
Published: December 2021

AbstractMiliarial gout is a rare clinical variant of chronic tophaceous gout characterised by tiny milia‐like papules containing chalky tophaceous material. In this report, we present a case of miliarial gout in a patient with known history of gouty arthritis and review the reported cases of miliarial gout in the literature to discuss its characteristics, diagnosis and treatment.
Grenz ray therapy in disseminated superficial actinic porokeratosis: A case series of 17 patients
Authors: Ting Sarajane , Webster Michael 
Published: December 2021

AbstractThe treatments available for disseminated superficial actinic porokeratosis (DSAP) have been limited and have variable efficacy. We report the largest case series to date of the use of Grenz ray therapy in 17 patients with DSAP. There was at least 50% improvement in DSAP lesions in all cases. Erythema, itching and burning were common side effects of Grenz ray therapy. We believe that Grenz ray therapy may be an effective treatment option for patients with DSAP.
Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review
Authors: Nestor C. C. , Ng C. , Sepulveda P. , Irwin M. G. 
Published: December 2021

SummaryVarious techniques have been explored to prolong the duration and improve the efficacy of local anaesthetic nerve blocks. Some of these involve mixing local anaesthetics or adding adjuncts. We did a literature review of studies published between 01 May 2011 and 01 May 2021 that studied specific combinations of local anaesthetics and adjuncts. The rationale behind mixing long‐ and short‐acting local anaesthetics to hasten onset and extend duration is flawed on pharmacokinetic principles. Most local anaesthetic adjuncts are not licensed for use in this manner and the consequences of untested admixtures and adjuncts range from making the solution ineffective to potential harm. Pharmaceutical compatibility needs to be established before administration. The compatibility of drugs from the same class cannot be inferred and each admixture requires individual review. Precipitation on mixing (steroids, non‐steroidal anti‐inflammatory drugs) and subsequent embolisation can lead to serious adverse events, although these are rare. The additive itself or its preservative can have neurotoxic (adrenaline, midazolam) and/or chondrotoxic properties (non‐steroidal anti‐inflammatory drugs). The prolongation of block may occur at the expense of motor block quality (ketamine) or block onset (magnesium). Adverse effects for some adjuncts appear to be dose‐dependent and recommendations concerning optimal dosing are lacking. An important confounding factor is whether studies used systemic administration of the adjunct as a control to accurately identify an additional benefit of perineural administration. The challenge of how best to prolong block duration while minimising adverse events remains a topic of interest with further research required.
Objective confirmation of asthma diagnosis, treatment adherence and patient outcomes in children and adolescents
Authors: Aarestrup Louise K. , Hermansen Mette N. , Prahl Julie , Hansen Kirsten S. , Chawes Bo L. 
Published: December 2021

AbstractAimThe aim of this study was to investigate the diagnostic workup in children with asthma hypothesising that objective confirmation of the diagnosis is associated with improved treatment adherence and patient outcomes.MethodsWe reviewed medical records of children aged 5–18 years diagnosed with asthma at the Department of Paediatric and Adolescent Medicine, Herlev‐Gentofte Hospital, Denmark, in 2018. Objective confirmation of the diagnosis was based on either (1) lung function, (2) bronchodilator response, (3) bronchial hyperresponsiveness and/or (4) elevated FeNO and was associated with treatment adherence (proportion of days covered, PDC), lung function development and exacerbations during a two‐year follow‐up period.ResultsA total of 88 children were included. Asthma was objectively confirmed in 67 (76%). Children with objective confirmation of the diagnosis were more likely to redeem short‐acting beta‐2‐agonist prescriptions: at least once, aOR = 1.3 (95% CI, 1.1–13.1), p = 0.036, and were more adherent to inhaled corticosteroid treatment: PDC>80%, aOR = 10.4 (1.8–201.1), p = 0.033. Further, objective confirmation was associated with improved lung function and reduced bronchodilator response, but not with exacerbations.ConclusionObjective confirmation of the asthma diagnosis in children is associated with an increased treatment adherence and improved lung function, which underlines the importance of conducting objective tests in the diagnostic workup in paediatric asthma management.
“Uncivilized children” or “victims of dementia”: Interpretations of aggression in older assisted living tenants
Authors: Saj Danielle , Funk Laura M. , Gerbrandt Emily , Spencer Dale , Herron Rachel 
Published: December 2021

AbstractThis study explores interpretations of interpersonal aggression involving older adults, through an analysis of semi‐structured interview data from 13 assisted living (AL) tenants and 19 AL service and/or care workers. Differing relations (tenant‐tenant and tenant‐worker) shape the kinds of tenant actions experienced as problematic and/or aggressive. Tenants and workers invoke communal living, aging, and dementia as explanatory frames, in part to mitigate victimization experiences through normalization and neutralization. This was more prominent among workers, who are less able to enact empowering responses as they sought to keep working in difficult circumstances. Structural constraints, and the power and social hierarchies that contribute to victimization, generate interpretive responses that obscure fulsome and contextualized understandings of the problem while further reinforcing oppressive discourses including a sense of the inevitability of aggression in older adults–especially those living with dementia.
Extracutaneous neutrophilic infiltration of the spleen and lung associated with pyoderma gangrenosum of the skin
Authors: Arai Sakurako , Furukawa Nao , Takahama Makoto , Kodai Shintaro , Ishii Naomi , Nakagawa Hidenori , Yamasaki Tomoaki , Kusutani Nao , Maekawa Naoki , Fukai Kazuyoshi 
Published: December 2021

Abstract
We describe a patient with extracutaneous pyoderma gangrenosum (PG), who presented with chest pain. Histological examination showed extracutaneous neutrophilic infiltration of the spleen and lung, with later findings of PG.
Stress amongst paediatric dental postgraduate students in India: A mixed‐method approach
Authors: Asokan Sharath , Pollachi Ramakrishnan GeethaPriya , Ranganatham Kirthi Varshini , Viswanath Sudhandra , Sivasamy Shyam 
Published: December 2021

AbstractIntroductionDental profession is one of the most stressful healthcare occupations. Paediatric dental postgraduates face multifaceted challenges in their everyday practice. This study aimed to determine the sources of stress amongst paediatric dental postgraduate students in India using a mixed‐method approach.Materials and MethodsA sequential mixed‐methods approach was employed. In the quantitative phase, a cross‐sectional web‐based questionnaire survey was conducted amongst paediatric dental postgraduates in India using the “Google Forms application” link. Based on the Dental Environment Stress (DES) questionnaire, the stress PACT questionnaire which includes 35 items was framed and validated. This validated questionnaire was used in the survey. In the qualitative phase, one‐on‐one, semi‐structured telephone interviews were conducted amongst 12 postgraduates.ResultsA total of 422 participants took part in the quantitative survey. Academic and specialty‐related domains were found to be the significant causes of stress amongst the five domains (p < .001). The top three stressful factors were as follows: getting an ideal case for clinical exams (68.2%), financial resources for conferences, dissertation, short studies and publications (53.2%) and fear of unemployment after graduation (52.3%). Based on qualitative interviews, four themes were derived, namely choice of paediatric dentistry, postgraduate life experience, stress management and expected changes in postgraduate life.ConclusionPsychological well‐being of the student is an important factor that influences the overall performance of students. Identifying the stress factors and using appropriate coping strategies can help postgraduates achieve personal, academic and professional success.
Highly mixed impacts of near‐future climate change on stock productivity proxies in the North East Atlantic
Authors: Kjesbu Olav Sigurd , Sundby Svein , Sandø Anne Britt , Alix Maud , Hjøllo Solfrid Sætre , Tiedemann Maik , Skern‐Mauritzen Mette , Junge Claudia , Fossheim Maria , Thorsen Broms Cecilie , Søvik Guldborg , Zimmermann Fabian , Nedreaas Kjell , Eriksen Elena , Höffle Hannes , Hjelset Ann Merete , Kvamme Cecilie , Reecht Yves , Knutsen Halvor , Aglen Asgeir , Albert Ole Thomas , Berg Erik , Bogstad Bjarte , Durif Caroline , Halvorsen Kim Tallaksen , Høines Åge , Hvingel Carsten , Johannesen Edda , Johnsen Espen , Moland Even , Skuggedal Myksvoll Mari , Nøttestad Leif , Olsen Erik , Skaret Georg , Skjæraasen Jon Egil , Slotte Aril , Staby Arved , Stenevik Erling Kåre , Stiansen Jan Erik , Stiasny Martina , Sundet Jan H. , Vikebø Frode , Huse Geir 
Published: December 2021

AbstractImpacts of climate change on ocean productivity sustaining world fisheries are predominantly negative but vary greatly among regions. We assessed how 39 fisheries resources—ranging from data‐poor to data‐rich stocks—in the North East Atlantic are most likely affected under the intermediate climate emission scenario RCP4.5 towards 2050. This region is one of the most productive waters in the world but subjected to pronounced climate change, especially in the northernmost part. In this climate impact assessment, we applied a hybrid solution combining expert opinions (scorings)—supported by an extensive literature review—with mechanistic approaches, considering stocks in three different large marine ecosystems, the North, Norwegian and Barents Seas. This approach enabled calculation of the directional effect as a function of climate exposure and sensitivity attributes (life‐history schedules), focusing on local stocks (conspecifics) across latitudes rather than the species in general. The resulting synopsis (50–82°N) contributes substantially to global assessments of major fisheries (FAO, The State of World Fisheries and Aquaculture, 2020), complementing related studies off northeast United States (35–45°N) (Hare et al., PLoS One, 2016, 11, e0146756) and Portugal (37–42°N) (Bueno‐Pardo et al., Scientific Reports, 2021, 11, 2958). Contrary to prevailing fisheries forecasts elsewhere, we found that most assessed stocks respond positively. However, the underlying, extensive environmental clines implied that North East Atlantic stocks will develop entirely different depending upon the encountered stressors: cold‐temperate stocks at the southern and Arctic stocks at the northern fringes appeared severely negatively impacted, whereas warm‐temperate stocks expanding from south were found to do well along with cold‐temperate stocks currently inhabiting below‐optimal temperatures in the northern subregion.