bluuebunny/crossref_metadata_2025 huggingface dataset:
Lessons from insiders: Embracing subjectivity as objectivity in victimology
Authors: Marcoux Rouleau Alexis
Published: June 2023

Due to the prevalence of victimization in society, it is likely that many victimologists have been victimized or will be in their lifetimes. This poses a challenge for the field of victimology as traditional, positivist conceptions of ‘good science’ require researchers to be outsiders relative to populations they study. This paper asks: What are the epistemological and practical implications of victimological research conducted by researchers who have firsthand experiences of victimization? What lessons can be retained by other victimologists and researchers in general? How can these epistemological considerations be applied in practice? To answer these questions, I examine the meanings of insider and outsider status and the implications for objectivity and subjectivity as per positivist and standpoint epistemologies. I present the case of victimologists who have been victimized as well as the advantages and disadvantages of this form of insider research. I deconstruct insider–outsider, subjectivity–objectivity dualisms as they pertain to victimologists, concluding that all victimologists can be subjective whether they are technically insiders or not. In closing, I discuss how all victimologists can embrace their own and their participants’ subjectivity as a resource for objectivity by examining location, emotions and bodies, and ethics throughout the research process.
Two-year, real-world erenumab persistence and quality of life data in 82 pooled patients with abrupt onset, unremitting, treatment refractory headache and a migraine phenotype: New daily persistent headache or persistent post-traumatic headache in the majority of cases
Authors: Buture Alina , Tomkins Esther M. , Shukralla Arif , Troy Emma , Conaty Katie , Macken Esther , Lonergan Roisin , Melling Jane , Long Niamh , Birrane Kieran , Shaikh Eamonn , Goadsby Peter J. , Ruttledge Martin H.
Published: June 2023

Background

Patients diagnosed with New Daily Persistent Headache and Persistent Post-Traumatic Headache belong to a heterogeneous group of primary and secondary headache disorders, with the common clinical feature that these conditions start abruptly, continue unabated, and are refractory to conventional migraine preventive treatments.

Objective

This is a real-world, medium-term audit to explore whether erenumab improves quality of life in a pooled group of 82 abrupt-onset, unremitting and treatment refractory patients, where the diagnosis is new daily persistent headache and persistent post-traumatic headache in the majority of cases.

Methods

Eighty-two patients were treated with erenumab every 28 days over a two to three-year period, beginning in December 2018. These patients were “longstanding chronic” and refractory with a median of eight (IQR 4–12) prior failed migraine preventive treatments and median duration of disease of seven (IQR 3–11) years. The starting dose of erenumab was 70 mg in 79% of cases and 140 mg in the remaining patients (individuals with a BMI of more than 30). All patients were asked to complete three migraine specific Quality of Life questionnaires or Patient Reported Outcome Measures before starting treatment and typically at 3–12 intervals until the end of June 2021 or cessation of treatment. The Patient Reported Outcome Measures included: Headache Impact Test-6, Migraine Associated Disability Assessment test and Migraine-Specific Quality-of-Life Questionnaire. Patients generally only stayed on treatment after 6–12 months if there was deemed to be an improvement of at least 30% and there were no significant side effects. The longest treated cases have quality of life data for 30 months after starting erenumab.

Results

Of the 82 patients, 29 (35%) had improvement in Quality of Life scores, with no significant side effects, and wished to stay on treatment. Fifty-three patients (65%) stopped treatment during the first 6–25 months due to lack of efficacy and/or patient reported side effects ( n = 33 and n = 17, respectively) or a combination of both, pregnancy planning ( n = 2), and lost to follow up ( n = 1).

Conclusion

Significant improvements in Quality of Life scores were recorded by one-third of patients over a period of 11–30 months, with a 35% persistence after a median of 26 months of treatment. This contrasts with our recently published, treatment resistant, chronic migraine cohort where the persistence with erenumab treatment was almost 55% after a median time of 25 months.
The Power of Silence: Anxiety and Autonomy in TA Labor
Authors: Eby Margaret
Published: June 2023

When I took on increasing responsibilities within my university's pedagogical training programs during the pandemic, I expected an increase in collaboration and pedagogical discussion because of the difficult teaching circumstances. Instead, I came to see a silence that kept teaching assistants (TAs) from talking about their labor process either with their instructors or with fellow TAs. In this paper, I theorize this silence both as a defense against anxiety and as protecting autonomy. I draw on my own experiences as a TA, my work as a pedagogy instructor in my department and for the university, and an ethnography of working TAs to investigate how TAs leverage their silence to strategically manage multiple competing interests. Finally, I suggest that TAs first internalize these dual purposes of silence to make sense of their teaching labor and later carry it with them as they go from trainee to professional academic.
Street-Level Educators: The Selective Recognition of Students and Invisible TA Labor
Authors: Torres Carpio Elizabeth
Published: June 2023

Drawing on my experience as a teaching assistant (TA), I expand on Michael Lipsky's concept of the street-level bureaucrat by focusing on how an agency's construction of the client shapes the work of the bureaucrat. I call this selective recognition. The university classifies students into three types: the archetypal student for whom the university is designed, the partially recognized student who receives accommodations, and the unrecognized student with responsibilities that make learning difficult. The result is an adaptation of the TA's three dimensions of the labor process: teaching, administration, and care work. The labor contract stipulates the first and a modicum of the second but not the third. Changing student demographics have increased all dimensions of TA labor, especially administrative tasks and the amount of invisible care work performed. The extractive university relies on this invisible and often overextended labor to dampen and conceal the reality of its own failing mission.
Humans’ Bias Blind Spot and Its Societal Significance
Authors: Pronin Emily , Hazel Lori
Published: June 2023

Human beings have a bias blind spot. We see bias all around us but sometimes not in ourselves. This asymmetry hinders self-knowledge and fuels interpersonal misunderstanding and conflict. It is rooted in cognitive mechanics differentiating self- and social perception as well as in self-esteem motives. It generalizes across social, cognitive, and behavioral biases; begins in childhood; and appears across cultures. People show a bias blind spot in high-stakes contexts, including investing, medicine, human resources, and law. Strategies for addressing the problem are described.
Reversible positioning head tilt observed in 14 cats with hypokalaemic myopathy
Authors: Tamura Shinji , Nakamoto Yuya , Tamura Yumiko
Published: June 2023

Case series summary

Positioning head tilt (PHT) is a dynamic neurological sign in which the head tilts to the opposite side to which it is moving. This sign is triggered in response to head movement and is thought to be due to the lack of inhibition of vestibular nuclei by the cerebellar nodulus and uvula (NU). The occurrence of PHT in animals has been suggested to be an indicator of NU dysfunction. Here, we describe the acute onset of PHT in 14 cats. All the cats were diagnosed with hypokalaemic myopathy caused by a range of pathologies. The PHT resolved along with other signs related to myopathy, such as cervical flexion and generalised weakness, after electrolyte correction in all cats.

Relevance and novel information

Hypokalaemic myopathy was the likely cause of PHT in the present feline cases.
Glial fibrillary acidic protein and multiple sclerosis progression independent of acute inflammation
Authors: Jiang Xiaotong , Shen Changyu , Teunissen Charlotte E , Wessels Mark , Zetterberg Henrik , Giovannoni Gavin , Singh Carol M , Caba Bastien , Elliott Colm , Fisher Elizabeth , de Moor Carl , Belachew Shibeshih , Gafson Arie R
Published: June 2023

Background:

The clinical relevance of serum glial fibrillary acidic protein (sGFAP) concentration as a biomarker of MS disability progression independent of acute inflammation has yet to be quantified.

Objective:

To test whether baseline values and longitudinal changes in sGFAP concentration are associated with disability progression without detectable relapse of magnetic resonance imaging (MRI) inflammatory activity in participants with secondary-progressive multiple sclerosis (SPMS).

Methods:

We retrospectively analyzed longitudinal sGFAP concentration and clinical outcome data from the Phase 3 ASCEND trial of participants with SPMS, with no detectable relapse or MRI signs of inflammatory activity at baseline nor during the study ( n = 264). Serum neurofilament (sNfL), sGFAP, T2 lesion volume, Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW), 9-Hole Peg Test (9HPT), and composite confirmed disability progression (CDP) were measured. Linear and logistic regressions and generalized estimating equations were used in the prognostic and dynamic analyses.

Results:

We found a significant cross-sectional association between baseline sGFAP and sNfL concentrations and T2 lesion volume. No or weak correlations between sGFAP concentration and changes in EDSS, T25FW, and 9HPT, or CDP were observed.

Conclusion:

Without inflammatory activity, changes in sGFAP concentration in participants with SPMS were neither associated with current nor predictive of future disability progression.
Muslim women in the workplace and the Equality Act 2010: Opportunities for an intersectional analysis
Authors: Cannon Catriona
Published: June 2023

The interplay of religion and gender is a relevant factor in the labour market disadvantage experienced by Muslim women. Despite widespread recognition of the importance of addressing disadvantage through an intersectional lens, the domestic equality law framework in Britain continues to adopt fixed and discrete classifications of status inequality, undermining protection for Muslim women in the workplace. This paper uses doctrinal and socio-legal method to expose the disregard in the application of British equality law in its international human rights context to the interaction of religion with gender and to present opportunities for development through case law of an intersectional analysis of disadvantage. After highlighting the labour market disadvantage experienced by Muslim women and making the case for an intersectional response, the paper will assess the application of the British equality law framework in relevant cases and will highlight its contribution to the emergence of a ‘conflict’ narrative. This paper will argue that there is, however, scope in human rights, proportionality and harm analyses to highlight experiences of discrimination at the vector of religion and gender. It will conclude that litigants who avail of these opportunities can contribute to development of law and policy which better reflects lived experience.
Disconnective action: Online activism against a corporate sponsorship at WorldPride 2021
Authors: Just Sine Nørholm , Christensen Jannick Friis , Schwarzkopf Stefan
Published: June 2023

Disconnective action, this article argues, is an important supplement to the logic of connective action, which enables social movements to organize informally online. Through the (threat of) disconnection, members may (re)assert their agency in relation to social movement organizations. In conducting a case study of LGBTI+ community members’ protests of a corporate sponsorship of WorldPride 2021, we establish disconnective action as a particular form of within-movement activism that relies both on social media affordances and the conditions of possibility of hybrid media ecologies. Thus, we explore how individual members of the LGBTI+ community were able to influence the formal organization of WorldPride 2021, as the threat of community members’ disconnection from the event led the organizers to terminate a corporate sponsorship. On this basis, we conceptualize disconnective action as a central means for individual activists to shape the movements of which they are part.
Postoperative Functional Assessment in Patients with Tumors Around the Knee Treated with Endoprosthetic Reconstruction: A Multicenter Retrospective Cohort Study
Authors: Zhao Yun-long , Zhang Hao-ran , Zhang Jing-yu , Hu Yong-cheng
Published: June 2023

Objectives

The restoration of as much normal function as possible has become an important goal following the endoprosthetic reconstruction. The objective of this study was to assess the functional outcome after endoprosthetic reconstruction for tumors around the knee and to explore prognostic factors of functional outcome.

Methods

We retrospectively collected data on patients who underwent tumor prosthetic replacements consecutively. Musculoskeletal Tumour Society score and Toronto Extremity Salvage Score were used to assess the functional outcome at 1, 3, 6, 12, and 24 months after surgery. The logistic model was used to select factors that had potential predictive value for postoperative function. Potential prognostic factors included age, gender, tumor site, type of tumor, length of bone resection, type of prosthesis, length of prosthetic stem, chemotherapy, pathological fracture, and body mass index.

Results

At the 24 months after surgery, the mean musculoskeletal tumor society (MSTS) score was 81.4% and the mean Toronto extremity salvage score (TESS) was 83.6%. At the last follow-up, 68% of patients and 73% of patients received perfect or good MSTS score and TESS score, respectively. The multivariate analysis according to ordered-logit model showed that age < 35 years, distal femoral prosthesis, and length of bone resection < 14 cm were independent prognostic factors of better functional outcome.

Conclusions

Endoprosthetic reconstruction may provide good functional results for most patients. Younger patients with distal femoral prosthesis and shorter resection of bone (on the premise of complete resection of tumor) are more likely to obtain satisfactory functional results after surgery.
Understanding the Third Reich by Means of the Law: The Decisions of the Supreme Restitution Court for Berlin as Sources on the Holocaust and the Development of Holocaust Interpretations
Authors: Balz Eva
Published: June 2023

This article introduces the decisions of the Oberstes Rückerstattungsgericht für Berlin (Supreme Restitution Court for Berlin) as historical sources that contribute to a better understanding of how early interpretations of the Holocaust developed. The Oberstes Rückerstattungsgericht für Berlin was established in 1953 as the final court of appeals for restitution matters in West Berlin. Some of its decisions were published in a collection that would later be used by judges, lawyers and claimants. Legal experts and practitioners who dealt with restitution would also discuss these decisions extensively. As no other means of gathering insight into the Oberstes Rückerstattungsgericht für Berlin's work were available, its publications became the most important communicative channel for actors within the Court's jurisdiction. The decisions contained distinct narratives concerning the Third Reich that stressed the importance of authoritative political structures while also focussing on state agencies and the Nationalsozialistische Deutsche Arbeiterpartei as main actors. The accounts given in the decisions were partly based on analyses of historical records that were performed either by the judges themselves or by historians at the Institut für Zeitgeschichte in Munich (Institute for Contemporary History). This article suggests that on a broader societal level, the decisions contributed to the dissemination of state-centred ideas about the Holocaust. At the same time, the text draws attention to their complicated genesis. Situating the emergence of the decisions alongside the concrete implementation of restitution laws, the Cold War in Berlin and Vergangenheitspolitik (politics of the past), I demonstrate that the perpetuation of state-focussed historical concepts, to a large extent, resulted from the judges’ desire to lessen their significant workloads and to work without the interference of political actors.
Blasting vibration hazard classification and prediction research
Authors: Zhang Guangquan , Wang Mengjia , Yang Ruzi , Si Kaikai
Published: June 2023

This paper explores the hazard classification method of blasting vibration on nearby buildings. The ratio of the self-vibration frequency f0 of the protected buildings to the main vibration frequency f of blasting vibration and the ratio of the actual measured peak blasting vibration velocity to the permissible vibration velocity of blasting safety regulations are used as two indicators of the blasting vibration hazard classification method, the blasting vibration hazard index calculation formula was proposed, and the blasting vibration hazard was classified into four levels according to the blasting vibration hazard index. An open pit mine blasting project was used for monitoring, the collected data were processed by random forest method. After processing, bursting heart distance, the total explosive quantity required for one blast, the hole distance meter delay, and the row distance meter delay was selected as the input parameters; the optimal kernel function parameter gamma and c were applied to the SVR (Support Vector Regression) model by changing the search step to expand the parameter search, and improved GS-SVR (Grid Search-Support Vector Regression) model was constructed, through which peak blasting vibration velocity and vibration frequency values were predicted. The results show: improved GS-SVR is effective in predicting peak blasting vibration velocity, with the lowest relative error of 0.15% and the average error of 7.96%; the minimum relative error for the prediction of vibration frequency is 0.03% and the average error is 2.54%. The measured data in the literature of related scholars verified that the blasting vibration hazard classification method is scientific and feasible. It can provide reference and reference for blasting vibration hazard classification and prediction of similar blasting projects.
Generalisation of unpredictable action-effect features: Large individual differences with little on-average effect
Authors: Janczyk Markus , Miller Jeff
Published: June 2023

Ideomotor theory suggests that selecting a response is achieved by anticipating the consequences of that response. Evidence for this is the response-effect compatibility (REC) effect, that is, responding tends to be faster when the (anticipated) predictable consequences of a response (the action effects) are compatible rather than incompatible with the response. The present experiments investigated the extent to which the consequences must be exactly versus categorically predictable. According to the latter, an abstraction from particular instances to the categories of dimensional overlap might take place. For participants in one group of Experiment 1, left-hand and right-hand responses produced compatible or incompatible action effects in perfectly predictable positions to the left or right of fixation, and a standard REC effect was observed. For participants in another group of Experiment 1, as well as in Experiments 2 and 3, the responses also produced action effects to the left or right of fixation, but the eccentricity of the action effects (and thus their precise location) was unpredictable. On average, the data from the latter groups suggest that there is little, if any, tendency for participants to abstract the critical left/right features from spatially somewhat unpredictable action effects and use them for action selection, although there were large individual differences in these groups. Thus, at least on average across participants, it appears that the spatial locations of action effects must be perfectly predictable for these effects to have a strong influence on the response time.
Investors’ Irrational Sentiment and Stock Market Returns: A Quantile Regression Approach Using Indian Data
Authors: Yadav Yamini , Naik Pramod Kumar
Published: June 2023

Studying sentiment is crucial for investors and portfolio managers to determine whether sentiment can be used as information to make profits. This study examines the relationship between irrational sentiment among investors and excess returns in the Indian stock market using monthly data from July 2001 to December 2019. The study constructs a composite sentiment index that includes condensed information from 10 variables. The empirical analysis reveals that the influence of irrational sentiment among investors on excess returns in the stock market is not uniform across quantiles. Specifically, our results indicate that the irrational sentiment index has information regarding contemporaneous (future) variation in excess returns in upper (all) quantiles. Results also suggest that the predictive ability of irrational sentiment is enhanced when market conditions are right. We also decompose the sentiment into positive and negative irrational sentiment and find an asymmetrical impact in upper quantiles but lost at lower quantiles.
bELonging: Do Students Classified as English Learners Feel Included?
Authors: White Rachel S. , Schneider Jack , Mavrogordato Madeline
Published: June 2023

In this article, we analyze student survey data related to sense of belonging and relationships with teachers and adults within and across the fastest growing subgroup of K–12 public school students: students classified as English learners (ELs). Students classified as ELs in our study, overall, felt a similar sense of belonging, or slightly higher sense of belonging than their never and formerly EL-classified peers; however, within the sense of belonging constructs, students classified as ELs varied in their perceptions of school climate. Additionally, current EL-classified students who took the survey in English were more positive than those who took the survey in another language; however, once student demographics and school contexts were held constant, survey language was weakly related to our outcome measures. We conclude by discussing how our findings can guide K–12 education policies, practices, and research to foster inclusive educational environments.
Labral Pull-Through Technique for Arthroscopic Labral Reconstruction of the Hip
Authors: Looney Austin M. , Doran James P. , Johnson Emma E. , Salvo John P.
Published: June 2023

Background:

The goal of hip labral reconstruction is to restore the suction seal, requiring the labral graft to be precisely secured along the acetabular rim. When performed arthroscopically, controlling the graft as it is suspended in the hip joint between 2 cannulas can be challenging, making fixation in the optimal position to restore the suction seal difficult to achieve.

Indications:

Labral reconstruction/augmentation is indicated for patients with a deficient/dysfunctional labrum when repair alone cannot restore/maintain the suction seal.

Technique Description:

Following diagnostic arthroscopy, debridement, and measurement of the labral deficiency (30 mm), 70 mm tibialis anterior allograft was tubularized with a whipstitch and prepared with long suture tails at both ends and a single mattress stitch placed through the graft at the medial end. Holes for the anchors were pre-drilled. Viewing from the anterolateral portal, the graft was introduced down a sled through the modified anterior portal, pulled through the joint, and guided into the posterolateral portal cannula via instrumentation through the distal anterolateral accessory portal. With initial fixation achieved medially with the mattress stitch, directing the graft into position while achieving optimal coverage of the deficient area was facilitated by the excess graft length pulled into the posterolateral portal cannula.

Results:

Labral reconstruction can restore the suction seal of the hip joint when repair alone is not sufficient. Comparative studies with matched repair cohorts have demonstrated comparable survivorship and patient-reported outcomes between groups, with similar rates of patient acceptable symptomatic state and minimal clinically important difference between groups, and similar rates of return to sport in high-level athletes. Recent systematic reviews have largely corroborated these findings.

Discussion/Conclusions:

Arthroscopic labral reconstruction is an effective treatment option when repair alone cannot restore the suction seal when the graft is secured in an optimal position, but controlling the graft during passage and fixation while achieving a final length spanning the segmental deficiency in continuity with native tissue at both ends can present technical challenges. The labral pull-through technique greatly facilitates this process.

Patient Consent Disclosure Statement:

The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Development of a new seismic vulnerability model for churches based on simple typological features
Authors: Cescatti Elvis , Follador Veronica , Prota Andrea , da Porto Francesca
Published: June 2023

The sequence of seismic events occurred in last decades in Italy highlighted the high vulnerability of churches. Since the Umbria–Marche earthquake in 1997, a systematic series of post-earthquake surveys has been carried out. The data collected during those surveys were used to propose first sets of vulnerability and fragility curves. After the three last major earthquakes (L’Aquila 2009, Emilia 2012, Central Italy 2016–2017), other significant series of on-site surveys led to the collection of a large amount of data, both on the damage suffered by churches and their typological characteristics. In this study, a data set of 1127 churches damaged by the 2009 L’Aquila earthquake and the 2016–2017 Central Italy seismic sequence was analyzed. This article presents a new simplified approach to determine vulnerability indexes of churches, in order to obtain vulnerability curves, and then a set of fragility curves, depending on the typological characteristics of the single church. This allows to have a single set of curves with the entire sample and without a typological subdivision. This article first analyzes in detail the available database records to define their representativeness and influence on vulnerability. Then, a series of vulnerability modifiers are defined, pointing out which parameters effectively affect the overall vulnerability. These observations also allow identifying which parameters deserve to be collected onsite, improving the efficiency of future survey campaigns. In conclusion, starting from the vulnerability modifiers, a set of vulnerability and fragility curves are presented.
Data set from shaking table tests of a slender MDOF structure with base-rocking mechanisms
Authors: Zhong Chiyun , Christopoulos Constantin
Published: June 2023

Numerical models of seismic-resistant structures are typically validated by comparing numerically predicted key seismic response parameters to those obtained from benchmark shake table experiments. However, studies have shown that for structures rocking on rigid foundations, the seismic response can be unrepeatable in experiments and deterministically unpredictable by numerical models. Therefore, researchers have proposed to validate rigid rocking models using statistical approaches, yet no experimental study has examined whether the same observations apply to slender multi-degree-of-freedom (MDOF) free-rocking structures or controlled rocking structures with positive post-rocking stiffness and dedicated energy dissipation. This data paper describes the now publicly available data obtained from a series of 254 shaking table tests of a slender MDOF tower structure with two base-rocking mechanisms, which can be used to examine the predictability of the seismic response of an MDOF rocking structure and to statistically validate different approaches aiming to model tall and slender structures that utilize base-rocking mechanisms to mitigate the dynamic response due to higher-mode effects.
Five-year follow-up of KEYNOTE-087: pembrolizumab monotherapy for relapsed/refractory classical Hodgkin lymphoma
Authors: Armand Philippe , Zinzani Pier Luigi , Lee Hun Ju , Johnson Nathalie A. , Brice Pauline , Radford John , Ribrag Vincent , Molin Daniel , Vassilakopoulos Theodoros P. , Tomita Akihiro , von Tresckow Bastian , Shipp Margaret A. , Herrera Alex F. , Lin Jianxin , Kim Eunhee , Chakraborty Samhita , Marinello Patricia , Moskowitz Craig H.
Published: June 2023

Previous analyses of the phase 2 KEYNOTE-087 (NCT02453594) trial of pembrolizumab monotherapy demonstrated effective antitumor activity with acceptable safety in patients with relapsed or refractory (R/R) classical Hodgkin lymphoma (cHL). However, long-term response durability and outcome of patients who receive a second course after treatment discontinuation after complete response (CR) remain of clinical interest. We present KEYNOTE-087 data after >5 years of median follow-up. Patients with R/R cHL and progressive disease (PD) after autologous stem cell transplantation (ASCT) and brentuximab vedotin (BV; cohort 1), salvage chemotherapy and BV without ASCT (cohort 2), or ASCT without subsequent BV (cohort 3), received pembrolizumab for ≤2 years. Patients in CR who discontinued treatment and subsequently experienced PD were eligible for second-course pembrolizumab. Primary end points were the objective response rate (ORR) using blinded central review and safety. The median follow-up was 63.7 months. ORR was 71.4% (95% confidence interval [CI], 64.8-77.4; CR, 27.6%; partial response, 43.8%). Median duration of response (DOR) was 16.6 months; median progression-free survival was 13.7 months. A quarter of responders, including half of complete responders, maintained a response for ≥4 years. Median overall survival was not achieved. Among 20 patients receiving second-course pembrolizumab, ORR for 19 evaluable patients was 73.7% (95% CI, 48.8-90.8); median DOR was 15.2 months. Any-grade treatment-related adverse events occurred in 72.9% of patients and grade 3 or 4 adverse events occurred in 12.9% of patients; no treatment-related deaths occurred. Single-agent pembrolizumab can induce durable responses, particularly in patients achieving CR. Second-course pembrolizumab frequently reinduced sustained responses after relapse from initial CR.
Higher abatacept exposure after transplant decreases acute GVHD risk without increasing adverse events
Authors: Takahashi Takuto , Al-Kofahi Mahmoud , Jaber Mutaz , Bratrude Brandi , Betz Kayla , Suessmuth Yvonne , Yu Alison , Neuberg Donna S. , Choi Sung W. , Davis Jeffrey , Duncan Christine , Giller Roger , Grimley Michael , Harris Andrew C. , Jacobsohn David , Lalefar Nahal , Farhadfar Nosha , Pulsipher Michael A. , Shenoy Shalini , Petrovic Aleksandra , Schultz Kirk R. , Yanik Gregory A. , Blazar Bruce R. , Horan John T. , Watkins Benjamin , Langston Amelia , Qayed Muna , Kean Leslie S.
Published: June 2023

In the ABA2 study, the T-cell costimulation blockade agent, abatacept, was safe and effective in preventing acute graft-versus-host disease (aGVHD) after unrelated-donor hematopoietic cell transplant (HCT), leading to US Food and Drug Administration approval. Here, we performed a determination of abatacept pharmacokinetics (PK), which enabled an examination of how abatacept exposure-response relationships affected clinical outcomes. We performed a population PK analysis of IV abatacept using nonlinear mixed-effect modeling and assessed the association between abatacept exposure and key transplant outcomes. We tested the association between the trough after dose 1 (Ctrough_1) and grade (GR) 2 or 4 aGVHD (GR2-4 aGVHD) through day +100. An optimal Ctrough_1 threshold was identified via recursive partitioning and classification tree analysis. This demonstrated that abatacept PK was characterized by a 2-compartment model with first-order elimination. The ABA2 dosing regimen was based on previous work targeting a steady-state abatacept trough of 10 μg/mL. However, a higher Ctrough_1 (≥39 μg/mL, attained in ∼60% of patients on ABA2) was associated with a favorable GR2-4 aGVHD risk (hazard ratio, 0.35; 95% confidence interval, 0.19-0.65; P < .001), with a Ctrough_1 <39 μg/mL associated with GR2-4 aGVHD risk indistinguishable from placebo (P = .37). Importantly, no significant association was found between Ctrough_1 and key safety indicators, including relapse, and cytomegalovirus or Epstein-Barr virus viremia. These data demonstrate that a higher abatacept Ctrough_1 (≥39 μg/mL) was associated with a favorable GR2-4 aGVHD risk, without any observed exposure-toxicity relationships. This trial was registered at www.clinicaltrials.gov as #NCT01743131.
Reviewer Acknowledgement 2012
Authors: Menéndez-González Manuel
Published: June 2023

Contributing reviewers

The Editor-in-Chief of International Archives of Medicine would like to thank all our reviewers who have contributed to the journal in Volume 5 (2012).
Child-Sum EATree-LSTMs: enhanced attentive Child-Sum Tree-LSTMs for biomedical event extraction
Authors: Wang Lei , Cao Han , Yuan Liu , Guo Xiaoxu , Cui Yachao
Published: June 2023

Background

Tree-structured neural networks have shown promise in extracting lexical representations of sentence syntactic structures, particularly in the detection of event triggers using recursive neural networks.

Methods

In this study, we introduce an attention mechanism intoChild-Sum Tree-LSTMsfor the detection of biomedical event triggers. We incorporate previous researches on assigning attention weights to adjacent nodes and integrate this mechanism intoChild-Sum Tree-LSTMsto improve the detection of event trigger words. We also address a limitation of shallow syntactic dependencies inChild-Sum Tree-LSTMsby integrating deep syntactic dependencies to enhance the effect of the attention mechanism.

Results

Our proposed model, which integrates an enhanced attention mechanism into Tree-LSTM, shows the best performance for the MLEE and BioNLP’09 datasets. Moreover, our model outperforms almost all complex event categories for the BioNLP’09/11/13 test set.

Conclusion

We evaluate the performance of our proposed model with the MLEE and BioNLP datasets and demonstrate the advantage of an enhanced attention mechanism in detecting biomedical event trigger words.
Automatic generation of pseudoknotted RNAs taxonomy
Authors: Quadrini Michela , Tesei Luca , Merelli Emanuela
Published: June 2023

Background

The ability to compare RNA secondary structures is important in understanding their biological function and for grouping similar organisms into families by looking at evolutionarily conserved sequences such as 16S rRNA. Most comparison methods and benchmarks in the literature focus on pseudoknot-free structures due to the difficulty of mapping pseudoknots in classical tree representations. Some approaches exist that permit to cluster pseudoknotted RNAs but there is not a general framework for evaluating their performance.

Results

We introduce an evaluation framework based on a similarity/dissimilarity measure obtained by a comparison method and agglomerative clustering. Their combination automatically partition a set of molecules into groups. To illustrate the framework we define and make available a benchmark of pseudoknotted (16S and 23S) and pseudoknot-free (5S) rRNA secondary structures belonging to Archaea, Bacteria and Eukaryota. We also consider five different comparison methods from the literature that are able to manage pseudoknots. For each method we clusterize the molecules in the benchmark to obtain the taxa at the rank phylum according to the European Nucleotide Archive curated taxonomy. We compute appropriate metrics for each method and we compare their suitability to reconstruct the taxa.
Statistical methods and resources for biomarker discovery using metabolomics
Authors: Anwardeen Najeha R. , Diboun Ilhame , Mokrab Younes , Althani Asma A. , Elrayess Mohamed A.
Published: June 2023

Metabolomics is a dynamic tool for elucidating biochemical changes in human health and disease. Metabolic profiles provide a close insight into physiological states and are highly volatile to genetic and environmental perturbations. Variation in metabolic profiles can inform mechanisms of pathology, providing potential biomarkers for diagnosis and assessment of the risk of contracting a disease. With the advancement of high-throughput technologies, large-scale metabolomics data sources have become abundant. As such, careful statistical analysis of intricate metabolomics data is essential for deriving relevant and robust results that can be deployed in real-life clinical settings. Multiple tools have been developed for both data analysis and interpretations. In this review, we survey statistical approaches and corresponding statistical tools that are available for discovery of biomarkers using metabolomics.
Extreme plastomes in holoparasitic Balanophoraceae are not the norm
Authors: Kim Woorin , Lautenschläger Thea , Bolin Jay F. , Rees Mathew , Nzuzi Albertina , Zhou Renchao , Wanke Stefan , Jost Matthias
Published: June 2023

Background

Balanophoraceae plastomes are known for their highly condensed and re-arranged nature alongside the most extreme nucleotide compositional bias known to date, culminating in two independent reconfigurations of their genetic code. Currently, a large portion of the Balanophoraceae diversity remains unexplored, hindering, among others, evolutionary pattern recognition. Here, we explored newly sequenced plastomes of Sarcophyte sanguinea and Thonningia sanguinea. The reconstructed plastomes were analyzed using various methods of comparative genomics based on a representative taxon sampling.

Results

Sarcophyte, recovered sister to the other sampled Balanophoraceae s. str., has plastomes up to 50% larger than those currently published. Its gene set contains five genes lost in any other species, including matK. Five cis-spliced introns are maintained. In contrast, the Thonningia plastome is similarly reduced to published Balanophoraceae and retains only a single cis-spliced intron. Its protein-coding genes show a more biased codon usage compared to Sarcophyte, with an accumulation of in-frame TAG stop codons. Structural plastome comparison revealed multiple, previously unknown, structural rearrangements within Balanophoraceae.

Conclusions

For the “minimal plastomes” of Thonningia, we propose a genetic code change identical to sister genus Balanophora. Sarcophyte however differs drastically from our current understanding on Balanophoraceae plastomes. With a less-extreme nucleotide composition, there is no evidence for an altered genetic code. Using comparative genomics, we identified a hotspot for plastome reconfiguration in Balanophoraceae. Based on previously published and newly identified structural reconfigurations, we propose an updated model of evolutionary plastome trajectories for Balanophoraceae, illustrating a much greater plastome diversity than previously known.
Conducting school-based health surveys with secondary schools in England: advice and recommendations from school staff, local authority professionals, and wider key stakeholders, a qualitative study
Authors: Hatch Lorna M. , Widnall Emily C. , Albers Patricia N. , Hopkins Georgina L. , Kidger Judi , de Vocht Frank , Kaner Eileen , van Sluijs Esther M. F. , Fairbrother Hannah , Jago Russell , Campbell Rona M.
Published: June 2023

Background

Improving the health and well-being of young people is a public health priority. Schools present an ideal setting to implement strategies to improve young people’s health and well-being. A key strategy involves conducting surveys to assess student health needs, inform interventions, and monitor health over time. Conducting research in schools is, however, challenging. Schools can find it difficult to participate and adhere to research processes, even when they are keen to be involved in research, because of competing priorities (e.g., attendance and educational achievement), as well as time and resource constraints. There is a lack of literature on the perspectives of school staff and other key stakeholders working in young people’s health on how best to work with schools to conduct health research, and in particular, health surveys.

Methods

Participants (n = 26) included members of staff from 11 secondary schools (covering students aged 11–16 years), 5 local authority professionals, and 10 wider key stakeholders in young people's health and well-being (e.g., a school governor, a national government member), based in South West England. Participants took part in semi-structured interviews that were conducted either over the phone or via an online platform. Data were analysed using the Framework Method.

Results

Three main themes were identified: Recruitment and Retention, Practicalities of Data Collection in Schools, and Collaboration from Design to Dissemination. It is important to acknowledge the role of local authorities and academy trusts in the English education system, and work closely with these when conducting school-based health surveys. School staff prefer to be contacted about research via email and in the summer term, following exams. Researchers should contact a member of staff involved in student health/well-being, as well as senior leadership, during recruitment. Data collection during the start and end of the school year is undesirable. Research should be collaborative with school staff and young people, consistent with school priorities and values, and flexible and tailored to school timetables and resources.

Conclusions

Overall the findings demonstrate that survey-based research methods should be school-led and tailored to each school.
Mitochondrial DNA quantification correlates with the developmental potential of human euploid blastocysts but not with that of mosaic blastocysts
Authors: Luo Wen , Zheng Yi-Min , Hao Yan , Zhang Ying , Zhou Ping , Wei Zhaolian , Cao Yunxia , Chen Dawei
Published: June 2023

Purpose

We aimed to study the association between adjusted mtDNA levels in human trophectoderm biopsy samples and the developmental potential of euploid and mosaic blastocysts.

Methods

We analyzed relative mtDNA levels in 2,814 blastocysts obtained from 576 couples undergoing preimplantation genetic testing for aneuploidy from June 2018 to June 2021. All patients underwent in vitro fertilization in a single clinic; the study was blinded—mtDNA content was unknown at the time of single embryo transfer. The fate of the euploid or mosaic embryos transferred was compared with mtDNA levels.

Results

Euploid embryos had lower mtDNA than aneuploid and mosaic embryos. Embryos biopsied on Day 5 had higher mtDNA than those biopsied on Day 6. No difference was detected in mtDNA scores between embryos derived from oocytes of different maternal ages. Linear mixed model suggested that blastulation rate was associated with mtDNA score. Moreover, the specific next-generation sequencing platform used have a significant effect on the observed mtDNA content. Euploid embryos with higher mtDNA content presented significantly higher miscarriage rates and lower live birth rates, while no significant difference was observed in the mosaic cohort.

Conclusion

Our results will aid in improving methods for analyzing the association between mtDNA level and blastocyst viability.
Establishment and validation of a nomogram based on coagulation parameters to predict the prognosis of pancreatic cancer
Authors: Yunpeng Peng , Lingdi Yin , Xiaole Zhu , Dongya Huang , Le Hu , Zipeng Lu , Kai Zhang , Chaoqun Hou , Yi Miao , Feng Guo , Qiang Li
Published: June 2023

Background

In recent years, multiple coagulation and fibrinolysis (CF) indexes have been reported to be significantly related to the progression and prognosis of some cancers.

Objective

The purpose of this study was to comprehensively analyze the value of CF parameters in prognosis prediction of pancreatic cancer (PC).

Methods

The preoperative coagulation related data, clinicopathological information, and survival data of patients with pancreatic tumor were collected retrospectively. Mann Whitney U test, Kaplan-Meier analysis, and Cox proportional hazards regression model were applied to analyze the differences of coagulation indexes between benign and malignant tumors, as well as the roles of these indexes in PC prognosis prediction.

Results

Compared with benign tumors, the preoperative levels of some traditional coagulation and fibrinolysis (TCF) indexes (such as TT, Fibrinogen, APTT, and D-dimer) were abnormally increased or decreased in patients with pancreatic cancer, as well as Thromboelastography (TEG) parameters (such as R, K, α Angle, MA, and CI). Kaplan Meier survival analysis based on resectable PC patients showed that the overall survival (OS) of patients with elevated α angle, MA, CI, PT, D-dimer, or decreased PDW was markedly shorter than other patients; moreover, patients with lower CI or PT have longer disease-free survival. Further univariate and multivariate analysis revealed that PT, D-dimer, PDW, vascular invasion (VI), and tumor size (TS) were independent risk factors for poor prognosis of PC. According to the results of modeling group and validation group, the nomogram model based on independent risk factors could effectively predict the postoperative survival of PC patients.

Conclusion

Many abnormal CF parameters were remarkably correlated with PC prognosis, including α Angle, MA, CI, PT, D-dimer, and PDW. Furthermore, only PT, D-dimer, and PDW were independent prognostic indicators for poor prognosis of PC, and the prognosis prediction model based on these indicators was an effective tool to predict the postoperative survival of PC.