bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological and clinical impact of membrane EGFR expression in a subgroup of OC patients from the phase IV ovarian cancer MITO-16A/MANGO-OV2A trial
Authors: Forlani Luca , De Cecco Loris , Simeon Vittorio , Paolini Biagio , Bagnoli Marina , Cecere Sabrina Chiara , Spina Anna , Citeroni Eleonora , Bignotti Eliana , Lorusso Domenica , Arenare Laura , Russo Daniela , De Angelis Carmine , Ardighieri Laura , Scognamiglio Giosuè , Del Sesto Michele , Tognon Germana , Califano Daniela , Schettino Clorinda , Chiodini Paolo , Perrone Francesco , Mezzanzanica Delia , Pignata Sandro , Tomassetti Antonella 
Published: April 2023

Abstract
Background
Validated prognostic biomarkers for anti-angiogenic therapy using the anti-VEGF antibody Bevacizumab in ovarian cancer (OC) patients are still an unmet clinical need. The EGFR can contribute to cancer-associated biological mechanisms in OC cells including angiogenesis, but its targeting gave disappointing results with less than 10% of OC patients treated with anti-EGFR compounds showing a positive response, likely due to a non adequate selection and stratification of EGFR-expressing OC patients.

Methods
EGFR membrane expression was evaluated by immunohistochemistry in a cohort of 310 OC patients from the MITO-16A/MANGO-OV2A trial, designed to identify prognostic biomarkers of survival in patients treated with first line standard chemotherapy plus bevacizumab. Statistical analyses assessed the association between EGFR and clinical prognostic factors and survival outcomes. A single sample Gene Set Enrichment-like and Ingenuity Pathway Analyses were applied to the gene expression profile of 195 OC samples from the same cohort. In an OC in vitro model, biological experiments were performed to assess specific EGFR activation.

Results
Based on EGFR-membrane expression, three OC subgroups of patients were identified being the subgroup with strong and homogeneous EGFR membrane localization, indicative of possible EGFR out/in signalling activation, an independent negative prognostic factor for overall survival of patients treated with an anti-angiogenic agent. This OC subgroup resulted statistically enriched of tumors of histotypes different than high grade serous lacking angiogenic molecular characteristics. At molecular level, among the EGFR-related molecular traits identified to be activated only in this patients’ subgroup the crosstalk between EGFR with other RTKs also emerged. In vitro, we also showed a functional cross-talk between EGFR and AXL RTK; upon AXL silencing, the cells resulted more sensitive to EGFR targeting with erlotinib.

Conclusions
Strong and homogeneous cell membrane localization of EGFR, associated with specific transcriptional traits, can be considered a prognostic biomarker in OC patients and could be useful for a better OC patients’ stratification and the identification of alternative therapeutic target/s in a personalized therapeutic approach.
“I've got a spring in my step” participants experience of action observation therapy and eccentric exercises, a telehealth study for mid‐portion Achilles Tendinopathy: a qualitative study
Authors: Ryan Deirdre , Rio Ebonie , O'Donoghue Grainne , O'Sullivan Cliona 
Published: April 2023

AbstractBackgroundQuantitative research has dominated the field of Achilles Tendinopathy. The use of qualitative research allows in‐depth exploration of participants' perspectives, offering great insight in the evaluation of a trial's processes, particularly when exploring a novel intervention such as Action Observation Therapy combined with eccentric exercises which has not been previously researched. This study aimed to qualitatively explore participants' experiences of partaking in a telehealth study including the acceptability of the intervention, motivators for participation, and perspectives on the trial processes.MethodA thematic analysis as guided by Braun and Clarke was used to analyse the semi‐structured interviews conducted on a purposive sample of participants with mid‐portion Achilles Tendinopathy who recently completed a pilot feasibility study. The study adhered to the criteria for reporting qualitative research guidelines (COREQ).Results/DiscussionSixteen participants were interviewed. The five themes identified were: (i) The impact of Achilles Tendinopathy is commonly not prioritised with ‘The acceptance and minimisation of pain’ as a sub‐theme (ii) Therapeutic alliance has the greatest impact on support (iii) Factors which influenced adherence (iv) Action Observation Therapy is valued and recommended (v) Recommendations for future interventions.ConclusionThis study provides insightful recommendations around; exploring the use of Action Observation Therapy in Achilles Tendinopathy, the relative importance of therapeutic alliance rather than mode of therapy delivery, and that sufferers of Achilles Tendinopathy may not prioritise health seeking for this condition.
Differential diagnosis and cause-specific treatment during out-of-hospital cardiac arrest: a retrospective descriptive study
Authors: Heikkilä Elina , Jousi Milla , Nurmi Jouni 
Published: April 2023

Abstract
Background
The cardiopulmonary resuscitation (CPR) guidelines recommend identifying and correcting the underlying reversible causes of out-of-hospital cardiac arrest (OHCA). However, it is uncertain how often these causes can be identified and treated. Our aim was to estimate the frequency of point of care ultrasound examinations, blood sample analyses and cause-specific treatments during OHCA.

Methods
We performed a retrospective study in a physician-staffed helicopter emergency medical service (HEMS) unit. Data on 549 non-traumatic OHCA patients who were undergoing CPR at the arrival of the HEMS unit from 2016 to 2019 were collected from the HEMS database and patient records. We also recorded the frequency of ultrasound examinations, blood sample analyses and specific therapies provided during OHCA, such as procedures or medications other than chest compressions, airway management, ventilation, defibrillation, adrenaline or amiodarone.

Results
Of the 549 patients, ultrasound was used in 331 (60%) and blood sample analyses in 136 (24%) patients during CPR. A total of 85 (15%) patients received cause-specific treatment, the most common ones being transportation to extracorporeal CPR and percutaneous coronary intervention (PCI) (n = 30), thrombolysis (n = 23), sodium bicarbonate (n = 17), calcium gluconate administration (n = 11) and fluid resuscitation (n = 10).

Conclusion
In our study, HEMS physicians deployed ultrasound or blood sample analyses in 84% of the encountered OHCA cases. Cause-specific treatment was administered in 15% of the cases. Our study demonstrates the frequent use of differential diagnostic tools and relatively infrequent use of cause-specific treatment during OHCA. Effect on protocol for differential diagnostics should be evaluated for more efficient cause specific treatment during OHCA.
The therapeutic window of intravenous immunoglobulin (IVIG) and its correlation with clinical outcomes in Kawasaki disease: a systematic review and meta-analysis
Authors: Li Zheng , Cai Jianghui , Lu Jing , Wang Mingju , Yang Chenmei , Zeng Zheng , Tang Qian , Li Jianhong , Tang Wen , Luo Huiling , Pan Gaofeng , Zeng Xingmao 
Published: April 2023

Abstract
Background
The optimal therapeutic window to start intravenous immunoglobulin (IVIG) for Kawasaki disease (KD) is highly debatable. We aimed to summarize the existing literature to evaluate the therapeutic window of IVIG treatment and its correlation with clinical outcomes in KD patients.

Methods
We searched the databases from inception to August 26, 2022, without language restrictions. The primary outcomes were initial IVIG resistance and coronary artery lesions (CALs) in acute phase. Secondary outcome was CALs during 1–2 months of follow-up.

Results
27 studies involving 41,139 patients were included in this study. Very low-quality evidence showed that the earlier IVIG treatment within 4 days had a higher IVIG-resistance rate (RR, 1.80; 95% CI, 1.50–2.15; P < .00001; I2 = 75%) than the late treatment. Very low-quality evidence showed that IVIG treatment for more than 7 days was associated with a higher risk of CALs in acute phase(RR, 0.57; 95% CI, 0.40–0.80; P = .001; I2 = 76%). There was a lower risk of CALs during 1–2 months follow-up for those who started IVIG administration within 10 days from the onset.

Conclusions
Overall, IVIG treatment within 7 days of illness seems to be the optimal therapeutic window of IVIG. IVIG treatment within 7 days is found to be effective for reducing the risk of coronary artery lesions and cardiac sequelae in KD patients. The early IVIG treatment within 4 days should be vigilant for the IVIG resistance although large multi-center randomized trials with well design are needed.
Effect of EIT-guided PEEP titration on prognosis of patients with moderate to severe ARDS: study protocol for a multicenter randomized controlled trial
Authors: Yuan Xueyan , Zhang Rui , Wang Yuxuan , Chen Dongyu , Chao Yali , Xu Jingyuan , Guo Lanqi , Liu Airan , Xie Jianfeng , Pan Chun , Yang Yi , Qiu Haibo , Liu Ling 
Published: April 2023

Abstract
Background
Acute respiratory syndrome distress (ARDS) is a clinical common syndrome with high mortality. Electrical impedance tomography (EIT)-guided positive end-expiratory pressure (PEEP) titration can achieve the compromise between lung overdistension and collapse which may minimize ventilator-induced lung injury in these patients. However, the effect of EIT-guided PEEP titration on the clinical outcomes remains unknown. The objective of this trial is to investigate the effects of EIT-guided PEEP titration on the clinical outcomes for moderate or severe ARDS, compared to the low fraction of inspired oxygen (FiO2)-PEEP table.

Methods
This is a prospective, multicenter, single-blind, parallel-group, adaptive designed, randomized controlled trial (RCT) with intention-to-treat analysis. Adult patients with moderate to severe ARDS less than 72 h after diagnosis will be included in this study. Participants in the intervention group will receive PEEP titrated by EIT with a stepwise decrease PEEP trial, whereas participants in the control group will select PEEP based on the low FiO2-PEEP table. Other ventilator parameters will be set according to the ARDSNet strategy. Participants will be followed up until 28 days after enrollment. Three hundred seventy-six participants will be recruited based on a 15% decrease of 28-day mortality in the intervention group, with an interim analysis for sample size re-estimation and futility assessment being undertaken once 188 participants have been recruited. The primary outcome is 28-day mortality. The secondary outcomes include ventilator-free days and shock-free days at day 28, length of ICU and hospital stay, the rate of successful weaning, proportion requiring rescue therapies, compilations, respiratory variables, and Sequential Organ Failure Assessment (SOFA).

Discussion
As a heterogeneous syndrome, ARDS has different responses to treatment and further results in different clinical outcomes. PEEP selection will depend on the properties of patients and can be individually achieved by EIT. This study will be the largest randomized trial to investigate thoroughly the effect of individual PEEP titrated by EIT in moderate to severe ARDS patients to date.

Trial registration
ClinicalTrial.gov NCT05207202. First published on January 26, 2022.
Functions and regulatory mechanisms of resting hematopoietic stem cells: a promising targeted therapeutic strategy
Authors: Tang Xinyu , Wang Zhenzhen , Wang Jingyi , Cui Siyuan , Xu Ruirong , Wang Yan 
Published: April 2023

AbstractHematopoietic stem cells (HSCs) are the common and essential precursors of all blood cells, including immune cells, and they are responsible for the lifelong maintenance and damage repair of blood tissue homeostasis. The vast majority (> 95%) of HSCs are in a resting state under physiological conditions and are only activated to play a functional role under stress conditions. This resting state affects their long-term survival and is also closely related to the lifelong maintenance of hematopoietic function; however, abnormal changes may also be an important factor leading to the decline of immune function in the body and the occurrence of diseases in various systems. While the importance of resting HSCs has attracted increasing research attention, our current understanding of this topic remains insufficient, and the direction of clinical targeted treatments is unclear. Here, we describe the functions of HSCs, analyze the regulatory mechanisms that affect their resting state, and discuss the relationship between resting HSCs and different diseases, with a view to providing guidance for the future clinical implementation of related targeted treatments.
Adolescent borderline personality traits and dyadic behavior shape mother-adolescent cortisol synchrony
Authors: Fleck Leonie , Fuchs Anna , Lerch Stefan , Möhler Eva , Koenig Julian , Resch Franz , Kaess Michael 
Published: April 2023

Abstract
Background
Associations between parent and child cortisol levels (“cortisol synchrony”) are often reported and positive synchrony may mark dyadic regulation on a physiological level. Although dyadic behavior during interaction and adolescent borderline personality disorder (BPD) traits are linked with individual and dyadic regulatory capacities, little is known about how both factors influence parent-adolescent cortisol synchrony. We hypothesized that cortisol synchrony would differ depending on behavioral synchrony, i.e., smooth reciprocal dyadic interaction patterns, adolescent BPD traits, and their interactions.

Methods
Multilevel state-trait modeling was implemented to investigate associations between concurrent mother-adolescent state cortisol and mother-adolescent average cortisol levels in a community sample of 76 mother-adolescent dyads. Three saliva samples were collected across interaction paradigms. Behavioral synchrony was observed, and adolescent BPD traits were evaluated using clinical interviews.

Results
First, behavioral synchrony and absence of BPD traits were linked with positive associations between adolescent and maternal state cortisol (positive synchrony), BPD traits with negative associations (negative synchrony). When interaction effects were examined, results were more nuanced. In low-risk dyads (higher behavioral synchrony, no BPD traits) asynchrony was found. When risk (BPD traits) and resource (higher behavioral synchrony) were combined, synchrony was positive. Lastly, in high-risk dyads (lower behavioral synchrony, adolescent BPD traits), negative synchrony was observed. Average adolescent and maternal cortisol levels were consistently positively associated in dyads with higher risk.

Conclusions
Positive dyadic interaction patterns are associated with positive state cortisol synchrony in mother-adolescent dyads and could buffer the effect of BPD traits, possibly supporting the process of physiological regulation.
Influence of low-velocity superficial layer on long-period basin-induced surface waves in eastern Osaka basin
Authors: Oprsal Ivo , Sekiguchi Haruko , Iwata Tomotaka , Burjanek Jan 
Published: April 2023

AbstractThe long-period strong ground motions with periods above 1 s have, in the case of farther or deeper earthquakes, potential to cause serious damage to structures with low eigen frequency, such as long bridges, oil tanks, or artificially damped structures, such as high-rise buildings. This work focuses on wave propagation due to the deep large earthquake representing rare deep damaging events of the region, with relatively sparse data coverage, studied for simple geological models computed by 2D finite differences. We model the wave propagation by finite differences using up-to-date 3D structural model of the Osaka basin. The strong surface waves in the region are not directly generated by these deep sources, but they originate by refraction mostly at the edges of the bedrock–sediments interface. The objective of this research is to model observed surface Love wave generated in the eastern part of the basin that propagates approximately westwards and is recorded by several surface stations. At these stations, the 3D finite-difference modeling provides a good fit with the observed surface wave in terms of waveform, amplitude, and arrival time for the most detailed 3D velocity model that contains topmost 50–250 m structure with the lowest S-wave velocities of 250 m/s. The semblance analysis of the synthetic wave field reveals that the respective synthetic surface wave is a result of interfering waves arriving in OSA and WOS stations from NE and SE directions. Performed tests reveal that such a synthetic wave field is extremely sensitive to the presence of the superficial 50—250 m thick low-velocity structure which is only a small fraction of the propagating surface wave length and occupies only part of the surface area. The ability to model the surface wave in terms of amplitude and time arrival validates the 3D structural model for long-period Osaka Bay earthquake scenario computations.
Graphical Abstract
Closed‐leg standing long leg radiographs can be a useful tool to assess whether the joint line is parallel to the ground in restricted kinematic alignment total knee arthroplasty
Authors: Kobayashi Takashi , Goto Kazumi , Otsu Masayoshi , Michishita Kazuhiko 
Published: April 2023

AbstractPurposeRestricted kinematic alignment (rKA) is a modified technique of kinematic alignment (KA) total knee arthroplasty (TKA) for patients with an outlier or atypical knee anatomy, striving to preserve the native knee joint line parallel to the ground in a bipedal stance. This study aimed to evaluate the accuracy of rKA TKA with a computed tomography (CT)‐based patient‐specific instrument (PSI) to achieve the preoperative plan with the joint line parallel to the ground level.MethodsUsing a CT‐based PSI, 74 closed‐leg standing long‐leg radiographs were obtained before and after rKA TKA. The hip‐knee‐ankle angle (HKA), joint line orientation angle (JLOA), lateral distal femoral angle (LDFA), and medial proximal tibial angle (MPTA) were measured. Bone resection accuracy was evaluated by postoperative HKA deviations from the planned alignment and joint line by postoperative JLOA deviations from the ground level.ResultsThe mean postoperative JLOA and HKA were 2.1° valgus (range, standard deviation: 6.0° valgus to 3.0° varus, 2.0) and 2.6° varus (3.5° valgus to 12.5° varus, 3.2), respectively. Postoperative JLOA and HKA were within ± 3° of the planned alignment for 69% and 86% of cases, respectively.ConclusionsDespite a static verification, we clarified how the joint line after rKA TKA was reproduced in the closed‐leg long leg radiographs to mimic the limb position during gait. However, this imaging method is not well‐established, and lack of long‐term survivorship and the relationship between joint line inclination and clinical outcomes represented limitations of this study.Level of evidenceLevel IV.
Update of global maps of Alisov’s climate classification
Authors: Shimabukuro Ryu , Tomita Tomohiko , Fukui Ken-ichi 
Published: April 2023

AbstractProposed in 1954, Alisov’s climate classification (CC) focuses on climatic changes observed in January–July in large-scale air mass zones and their fronts. Herein, data clustering by machine learning was applied to global reanalysis data to quantitatively and objectively determine air mass zones, which were then used to classify the global climate. The differences in air mass zones between two half-year seasons were used to determine climatic zones, which were then subdivided into continental or maritime climatic regions or according to east–west climatic differences. This study renews Alisov’s CC for the first time in almost 70 years and employs data-driven machine learning to establish a standard for causal CC based on air masses.
Investigating and preventing scientific misconduct using Benford’s Law
Authors: Eckhartt Gregory M. , Ruxton Graeme D. 
Published: April 2023

AbstractIntegrity and trust in that integrity are fundamental to academic research. However, procedures for monitoring the trustworthiness of research, and for investigating cases where concern about possible data fraud have been raised are not well established. Here we suggest a practical approach for the investigation of work suspected of fraudulent data manipulation using Benford’s Law. This should be of value to both individual peer-reviewers and academic institutions and journals. In this, we draw inspiration from well-established practices of financial auditing. We provide synthesis of the literature on tests of adherence to Benford’s Law, culminating in advice of a single initial test for digits in each position of numerical strings within a dataset. We also recommend further tests which may prove useful in the event that specific hypotheses regarding the nature of data manipulation can be justified. Importantly, our advice differs from the most common current implementations of tests of Benford’s Law. Furthermore, we apply the approach to previously-published data, highlighting the efficacy of these tests in detecting known irregularities. Finally, we discuss the results of these tests, with reference to their strengths and limitations.
Climate change impact on the healthcare provided to patients
Authors: Al-Marwani Sabah 
Published: April 2023

Abstract
Background
The last several years have shed light on the fact that changes in the global climate pose one of the greatest dangers to mankind and life on Earth. Even though a growing amount of attention is being paid to the acute consequences of climate change on human health, there is still very little that is recognized or understood about the impacts of climate change events on patient-related aspects, especially patient care and safety.

Aim
This study aims to fill the gap in the literature and provide a comprehensive synopsis and critical investigation of the effects of climate change on patient care and safety.

Methodology
This research is based on a narrative review which was more appropriate to provide a descriptive analysis of the topic of interest and to be suitable for the wide scope of the study. The research was conducted using several databases with no restriction on the date of the publication of searched documents and resulted in 34 articles which were then further assessed by removing any duplications and repetitions to have by the end 15 publications. The references of all included documents were further checked for additional relevant items. The study lasted for four months starting from 09/09/2022 to the last search date 10/01/2023.

Main results
Losing access to healthcare facilities, shortage in drugs due to disruption of supply chains resulting from climate extreme events, infections spread, increasing occurrence of medical errors, the emergence of new diseases, raising many problems with the safety of drug use, increasing patients vulnerability, delay in cancer detection and management, and worsening prognosis of cancer cases, are examples of the catastrophic effects that climate change poses on the health and patients care.

Conclusions
This study highlights the catastrophic impacts of climate change on patient care and safety and emphasizes the critical need for immediate action to reduce climate change and build more resilient healthcare systems.