bluuebunny/crossref_metadata_2025_split huggingface dataset:
HLA genotyping in Japanese patients with multiple myeloma receiving bortezomib: An exploratory biomarker study of JCOG1105 (JCOG1105A1)
Authors: Ri Masaki , Iida Shinsuke , Maruyama Dai , Sakabe Aya , Kamei Ryo , Nakashima Takuto , Tohkin Masahiro , Osaga Satoshi , Tobinai Kensei , Fukuhara Noriko , Miyazaki Kana , Tsukamoto Norifumi , Tsujimura Hideki , Yoshimitsu Makoto , Miyamoto Kenichi , Tsukasaki Kunihiro , Nagai Hirokazu 
Published: October 2021

AbstractBortezomib (Btz) shows robust efficacy in patients with multiple myeloma (MM); however, some patients experience suboptimal responses and show specific toxicities. Therefore, we attempted to identify specific HLA alleles associated with Btz‐related toxicities and response to treatment. Eighty‐two transplant‐ineligible patients with newly diagnosed MM enrolled in a phase II study (JCOG1105) comparing two less intensive melphalan, prednisolone, plus Btz (MPB) regimens were subjected to HLA typing. The frequency of each allele was compared between the groups, categorized based on toxicity grades and responses to MPB therapy. Among 82 patients, the numbers of patients with severe peripheral neuropathy (PN; grade 2 or higher), skin disorders (SD; grade 2 or higher), and pneumonitis were 16 (19.5%), 15 (18.3%), and 6 (7.3%), respectively. Complete response was achieved in 10 (12.2%) patients. Although no significant HLA allele was identified by multiple comparisons, several candidates were identified. HLA‐B*40:06 was more prevalent in patients with severe PN than in those with less severe PN (odds ratio [OR] = 6.76). HLA‐B*40:06 and HLA‐DRB1*12:01 were more prevalent in patients with SD than in those with less severe SD (OR = 7.47 and OR = 5.55, respectively). HLA‐DRB1*08:02 clustered in the group of patients with pneumonitis (OR = 11.34). Complete response was achieved in patients carrying HLA‐DQB1*03:02, HLA‐DQB1*05:01, and HLA‐DRB1*01:01 class II alleles. HLA genotyping could help predict Btz‐induced toxicity and treatment efficacy in patients with MM, although this needs further validation.
Parental engagement in early intervention for infants with cerebral palsy—A realist synthesis
Authors: Harniess Phillip Antony , Gibbs Deanna , Bezemer Jeff , Purna Basu Anna 
Published: October 2021

AbstractBackgroundEmphasis on parental engagement strategies within occupational therapy and physiotherapy early intervention (EI) programmes for infants at high risk of cerebral palsy (CP) has increased. This reflects consensus that increasing parent participation enhances treatment efficacy, potentially improving infant and parent outcomes. However, evaluation of parental engagement in EI is complex. Despite the growing application of parental engagement strategies, aligned with family‐centred care practice, theoretical evaluation is currently lacking within the literature. This realist synthesis aimed to identify component theories underlying EI strategies to support parental engagement and to use empirical findings to evaluate how these work in practice.MethodsRealist synthesis: Databases Medline, Embase, Amed, CINAHL and PsychInfo were searched (from February 1985 ‐ February 2020); further articles were sourced from reference lists. A data extraction form was used, and a Critical Appraisal Skills Programme tool was used to assess study rigour.ResultsTwenty‐six articles were included. Quality of relationships, parent education and intervention co‐design were the key themes related to parental engagement strategies. Findings indicate that constructive parent reasoning mechanisms of trust, belief, sense of control, perceived feasibility of home programme delivery and ultimately motivation are linked to the underlying intervention resources afforded by specific strategies (e.g., coaching pedagogy). These responses are precursors to engagement outcomes that include increased parental self‐efficacy and adherence. Importantly, parental self‐efficacy can initiate a process of change leading to improved parental confidence and anxiety.ConclusionsSensitively designed programme strategies, centred on relational quality between parent, infant and therapist, are fundamental for effective parent connection, involvement and investment within EI for infants with CP.
The consequences and outcomes associated with dental implants encroaching on adjacent teeth
Authors: Hamdoon Zaid , Talaat Wael , Aziz Ahmed , Abdul Sattar Abier , Kheder Waad , Jerjes Waseem 
Published: October 2021

AbstractBackgroundDental implant placement carries a risk of iatrogenic damage to adjacent root surfaces.PurposeTo classify and understand different types of trauma to the tooth root body by dental implants.Materials and MethodsThis prospective case series included 43 implants placed between February 2017 and June 2020 that had primary stability and were in a position that accidentally invaded the adjacent teeth. The type and degree of the injury were evaluated clinically and radiographically. Tenderness, mobility, and sensitivity tests of the injured teeth were conducted at different visits. Implant failure was confirmed by the presence of implant mobility during the healing period.ResultsOverall, 43 patients had root injuries due to dental implant surgeries. Regarding the 43 injured roots, 32 developed transient tenderness to percussion, 16 developed variable degrees of resorption in the cementum, three lost pulp sensitivity and one had persistent tenderness to percussion. No injured teeth were lost. In three patients, implant periapical lesions were confirmed radiographically as radiolucency near the apex of the involved implants. Out of the 43 implants, 11 failed and were removed within 6 months, with an implant failure rate of (25%).ConclusionsRoot damage after implant surgery varies depending on the type and severity of injury. Periodic clinical and radiographical examination is necessary to monitor root resorption and implant integration and to rule out pulp necrosis.
Sulcus fluid volume, IL‐6, and Il‐1b concentrations in periodontal and peri‐implant tissues comparing machined and laser‐microtextured collar/abutment surfaces during 12 weeks of healing: A split‐mouth RCT
Authors: Guarnieri Renzo , Miccoli Gabriele , Reda Rodolfo , Mazzoni Alessandro , Di Nardo Dario , Testarelli Luca 
Published: October 2021

AbstractObjectivesTo compare gingival tissue healing at surgically manipulated periodontal sites and at sites receiving implants and healing abutments with machined (MS) vs laser‐microtextured (LMS) surface placed with one‐stage protocol.Material and MethodsTwenty‐four non‐smoking patients each received two implants with one‐stage protocol in a split‐mouth design on the same jaw. In each patient, one implant with a MS collar and one immediate healing abutment with a MS, and one implant with a LMS collar and one immediate healing abutment with a LMS were used. Soft tissues healing at surgically manipulated periodontal tissues (T+) and at non‐surgically manipulated periodontal tissues (T‐) at MS implant sites and at LMS implant sites were compared by means of clinical and biochemical parameters at baseline and at 1–2–3–4–6–8 and 12 weeks.ResultsPD and BoP mean values were statistically higher in MS than LMS implant sites (p<0.05). During early healing phase (1–4 weeks), MS and LMS peri‐implant tissues and periodontal tissues at T(+) showed no statistically significant difference in crevicular fluid volume changes (p>0.05). Between 6 and 12 weeks, compared with T(+), no statistically significant difference in crevicular fluid volume and IL‐6 and IL‐1β concentrations was noted in LMS implant sites (p>0.05), while statistically significantly higher mean values were noted in MS implant sites (p<0.05).ConclusionsCompared with T(+) and T(‐), both MS and LMS implant sites presented a higher pro‐inflammatory state in the early phase after surgery (1–4 weeks). At 12 weeks, only MS implant sites kept a higher pro‐inflammatory state, while at LMS implant sites, it becomes similar to T(+) and T(‐).
Applying assessments of adaptive capacity to inform natural‐resource management in a changing climate
Authors: Thurman Lindsey L. , Gross John E. , Mengelt Claudia , Beever Erik A. , Thompson Laura M. , Schuurman Gregor W. , Hoving Christopher L. , Olden Julian D. 
Published: October 2021

AbstractAdaptive capacity (AC)—the ability of a species to cope with or accommodate climate change—is a critical determinant of species vulnerability. Using information on species’ AC in conservation planning is key to ensuring successful outcomes. We identified connections between a list of species’ attributes (e.g., traits, population metrics, and behaviors) that were recently proposed for assessing species’ AC and management actions that may enhance AC for species at risk of extinction. Management actions were identified based on evidence from the literature, a review of actions used in other climate adaptation guidance, and our collective experience in diverse fields of global‐change ecology and climate adaptation. Selected management actions support the general AC pathways of persist in place or shift in space, in response to contemporary climate change. Some actions, such as genetic manipulations, can be used to directly alter the ability of species to cope with climate change, whereas other actions can indirectly enhance AC by addressing ecological or anthropogenic constraints on the expression of a species’ innate abilities to adapt. Ours is the first synthesis of potential management actions directly linked to AC. Focusing on AC attributes helps improve understanding of how and why aspects of climate are affecting organisms, as well as the mechanisms by which management interventions affect a species’ AC and climate change vulnerability. Adaptive‐capacity‐informed climate adaptation is needed to build connections among the causes of vulnerability, AC, and proposed management actions that can facilitate AC and reduce vulnerability in support of evolving conservation paradigms.
Is fistulotomy with immediate sphincter reconstruction (FISR) a sphincter preserving procedure for high anal fistula? A systematic review and meta‐analysis
Authors: Iqbal Nusrat , Dilke Stella Maye , Geldof Jeroen , Sahnan Kapil , Adegbola Samuel , Bassett Paul , Tozer Philip 
Published: October 2021

AbstractAimThis systematic review aimed to assess the outcomes of fistulotomy or fistulectomy and immediate sphincter repair (FISR) in relation to healing, incontinence and sphincter dehiscence both overall and in patients with high anal fistulae.MethodsMedline, Embase and The Cochrane library were searched for studies of patients undergoing FISR for anal fistula. Data regarding healing, continence and sphincter dehiscence were extracted overall and for high anal fistulae. The DerSimonian‐Laird random‐effects method was used for pooled analysis, heterogeneity between studies was assessed based on the significance of between‐study heterogeneity, and on the size of the I2 value. Risk of bias was assessed using the Cochrane risk of bias tool and the Newcastle‐Ottawa scale.ResultsWe identified 21 studies evaluating 1700 patients. Pooled analysis of healing reached 93% (95% CI: 91%–95%, I2 = 51% p‐value for heterogeneity = 0.004), with continence disturbance and worsening continence reaching 11% (95% CI: 6%–18%, I2 = 87% p < 0.001) and 8% (95% CI: 4%–13%, I2 = 74% p < 0.001), respectively. Subgroup analysis according to fistula height could only be conducted on limited data. Pooled healing in high anal fistulae was 89% (95% CI: 84%–94%, I2 = 76% p < 0.001), 16% suffered disturbance of continence (95% CI: 7%–27%, I2 = 89% p < 0.001), 8% worsening continence from baseline (95% CI: 2%–16%, I2 = 80% p < 0.001) and 2% suffered sphincter dehiscence (95% CI: 0%–10%, I2 = 89% p < 0.001).ConclusionThe evidence suggests FISR is a safe, effective procedure. However, data are limited by inconsistencies in reporting of continence and definition of fistula height, particularly high anal fistulae. Significant heterogeneity means that outcomes in high fistulae remain uncertain.
Merkel cell carcinoma in a young man with AIDS‐related Kaposi sarcoma
Authors: Schiele Kristan , Kojder Priscilla Ly , Haynes Alex B. , Soldano Anthony , Jambusaria‐Pahlajani Anokhi 
Published: October 2021

AbstractMerkel cell carcinoma (MCC) is a rare, aggressive primary neuroendocrine carcinoma of the skin that can present in immunocompromised patients. Kaposi sarcoma (KS) is an indolent angioproliferative tumor associated with human herpesvirus 8 (HHV8). The concurrence of both MCC and KS is rare, and there have been limited cases reported in the literature. We present a rare case of concurrent MCC and KS in an immunocompromised patient. To our knowledge, this is the first report of MCC and KS described in the same histopathological specimen. A 37‐year‐old Black male with a history of recurrent AIDS‐related KS involving bilateral lower extremities was evaluated for a tender nodule on the left posterior leg. A punch biopsy was consistent with MCC. Magnetic resonance imaging brain and full‐body positron emission tomography/computed tomography (PET/CT) scan were without evidence of distant metastasis. The patient underwent wide local excision with negative margins and completed postoperative radiation therapy. However, he later developed cutaneous metastasis of MCC to the left medial thigh and excision revealed residual MCC with adjacent KS. Treatment is still ongoing with pembrolizumab for both KS and MCC.
Maternal cradling bias in baboons: The first environmental factor affecting early infant handedness development?
Authors: Boulinguez‐Ambroise Grégoire , Pouydebat Emmanuelle , Disarbois Éloïse , Meguerditchian Adrien 
Published: October 2021

AbstractThe most emblematic behavioral manifestation of human brain asymmetries is handedness. While the precise mechanisms behind the development of handedness are still widely debated, empirical evidences highlight that besides genetic factors, environmental factors may play a crucial role. As one of these factors, maternal cradling behavior may play a key role in the emergence of early handedness in the offspring. In the present study we followed 41 Papio anubis infants living in social groups with their mother for which direction (e.g., left‐ or right‐arm) and degree of maternal cradling‐side bias were available from a previous published study. We assessed hand preferences for an unimanual grasping task at three developmental stages: (A) 0–4, (B) 4—6, and (C) 9–10 months of age. We found that individual hand preferences for grasping exist as soon as the first months of age, with a population‐level left‐handedness predominance, being stable until 6 months; to wit the period during which juveniles are mainly carried by their mothers. More importantly, this early postnatal handedness is positively correlated with maternal cradling lateralization. Interestingly, hand preferences assessed later in the development, once juveniles are no longer carried (i.e., from 9 to 10 months of age), are less dependent from the maternal cradling bias and less consistent with the earlier developmental stages, especially in infants initially cradled on the right maternal side. Our findings suggest that the ontogenetic dynamics of the infant's hand preference and its changes might ultimately rely on the degree of infant dependence from the mother across development.
Prior task experience increases 5‐year‐old children's use of proactive control: Behavioral and pupillometric evidence
Authors: Yanaoka Kaichi , van't Wout Félice , Saito Satoru , Jarrold Christopher 
Published: October 2021

AbstractChildren engage cognitive control reactively when they encounter conflicts; however, they can also resolve conflicts proactively. Recent studies have begun to clarify the mechanisms that support the use of proactive control in children; nonetheless, sufficient knowledge has not been accumulated regarding these mechanisms. Using behavioral and pupillometric measures, we tested the novel possibility that 5‐year‐old children (N = 58) learn to use proactive control via the acquisition of abstract task knowledge that captures regularities of the task. Participants were assigned to either a proactive training group or a control training group. In the proactive training group, participants engaged in a training phase where using proactive control was encouraged, followed by a test phase using different stimuli where both proactive and reactive control could be used. In the control training group, participants engaged in a training phase where both cognitive control strategies could be used, followed by a similarly‐structured test phase using different stimuli. We demonstrated children in the control training group responded more quickly and accurately and showed greater cue‐related pupil dilation in the test phase than in the training phase. However, there were no differences in response times, accuracies, and pupil dilation between the proactive and control training groups in the training and test phases. These findings suggest that prior task experience, that goes beyond specific knowledge about the timing of task goal activation, can lead children to engage more proactive control endogenously, even if they are not directly encouraged to do so.
Adaptive ontogenetic shifts in larval responses to environmental cues
Authors: Brackley Allison , Lill John T. , Weiss Martha R. 
Published: October 2021

AbstractAlthough many organisms experience relatively predictable environmental conditions throughout development, others, as a result of ontogenetic changes, inhabit very different environments across life stages, requiring them to navigate into habitats or microhabitats that they have not previously encountered. For holometabolous insects, late instars must often locate a safe site before undergoing pupation. In Lepidoptera, many pre‐pupae cease feeding and wander in search of an appropriate pupation site; their preferences display a shift in behavioral responses to habitat‐specific environmental cues, relative to those of feeding larvae. Having previously determined that pre‐pupae of Epargyreus clarus (Cramer) (Lepidoptera: Hesperiidae) move from their Fabaceae host plant down into the leaf litter, where they construct a pupal refuge out of dried leaves and silk, we investigated the sensory cues used by E. clarus in selecting a pupation location. We further explored how responses to these cues vary between actively feeding larvae and non‐feeding pre‐pupae, both for individual insects and for stage‐based cohorts. Using Y‐tube assays, we determined that pre‐pupae used visual (light) and gravitational cues to move from host plants into the leaf litter, whereas the odor cues we tested did not appear to influence their decision‐making. Directional responses to both light and gravity reversed over ontogeny, allowing the two life stages to make use of the same cues to produce stage‐appropriate adaptive behaviors.
Multivariate patterns and long‐range temporal correlations of alpha oscillations are associated with flexible manipulation of visual working memory representations
Authors: Golemme Mara , Tatti Elisa , Di Bernardi Luft Caroline , Bhattacharya Joydeep , Herrojo Ruiz Maria , Cappelletti Marinella 
Published: October 2021

AbstractThe ability to flexibly manipulate memory representations is embedded in visual working memory (VWM) and can be tested using paradigms with retrospective cues. Although valid retrospective cues often facilitate memory recall, invalid ones may or may not result in performance costs. We investigated individual differences in utilising retrospective cues and evaluated how these individual differences are associated with brain oscillatory activity at rest. At the behavioural level, we operationalised flexibility as the ability to make effective use of retrospective cues or disregard them if required. At the neural level, we tested whether individual differences in such flexibility were associated with properties of resting‐state alpha oscillatory activity (8–12 Hz). To capture distinct aspects of these brain oscillations, we evaluated their power spectral density and temporal dynamics using long‐range temporal correlations (LRTCs). In addition, we performed multivariate patterns analysis (MVPA) to classify individuals' level of behavioural flexibility based on these neural measures. We observed that alpha power alone (magnitude) at rest was not associated with flexibility. However, we found that the participants' ability to manipulate VWM representations was correlated with alpha LRTC and could be decoded using MVPA on patterns of alpha power. Our findings suggest that alpha LRTC and multivariate patterns of alpha power at rest may underlie some of the individual differences in using retrospective cues in working memory tasks.
Topographical distance between presynaptic Ca2+ channels and exocytotic Ca2+ sensors contributes to differential facilitatory actions of roscovitine on neurotransmitter release at cerebellar glutamatergic and GABAergic synapses
Authors: Satake Shin' Ichiro , Konishi Shiro 
Published: October 2021

AbstractCalcium influx into presynaptic terminals through voltage‐gated Ca2+ channels triggers univesicular or multivesicular release of neurotransmitters depending on the characteristics of the release machinery. However, the mechanisms underlying multivesicular release (MVR) and its regulation remain unclear. Previous studies showed that in rat cerebellum, the cyclin‐dependent kinase inhibitor roscovitine profoundly increases excitatory postsynaptic current (EPSC) amplitudes at granule cell (GC)‐Purkinje cell (PC) synapses by enhancing the MVR of glutamate. This compound can also moderately augment the amplitude and prolong the decay time of inhibitory postsynaptic currents (IPSCs) at molecular layer interneuron (MLI)‐PC synapses via MVR enhancement and GABA spillover, thus allowing for persistent activation of perisynaptic GABA receptors. The enhanced MVR may depend on the driving force for Cav2.1 channel‐mediated Ca2+ influx. To determine whether the distinct spatiotemporal dynamics of presynaptic Ca2+ influence MVR, we compared the effects of slow and fast Ca2+ chelators, that is, EGTA and BAPTA, respectively, on roscovitine‐induced actions at GC‐PC and MLI‐PC synapses. Membrane‐permeable EGTA‐AM decreased GC‐PC EPSC and MLI‐PC IPSC amplitudes to a similar extent but suppressed the roscovitine‐induced enhancement of EPSCs. In contrast, BAPTA‐AM attenuated the effects of roscovitine on IPSCs. These results suggest that roscovitine augmented glutamate release by activating the release machinery located distally from the Cav2.1 channel clusters, while it enhanced GABA release in a manner less dependent on those at distal sites. Therefore, the spatial relationships among Ca2+ channels, buffers, and sensors are critical determinants of the differential facilitatory actions of roscovitine on glutamatergic and GABAergic synapses in the cerebellar cortex.