bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel preference-informed complementary trial (PICT) design for clinical trial research influenced by strong patient preferences
Authors: Ali Samina , Hopkin Gareth , Poonai Naveen , Richer Lawrence , Yaskina Maryna , Heath Anna , Klassen Terry Paul , McCabe Chris ,   on behalf of the KidsCAN PERC Innovative Pediatric Clinical Trials No OUCH Study Group, Drendel Amy , Hopkin Gareth , Round Jeff , Offringa Martin , Pechlivanoglou Petros , Pullenayegum Eleanor , Rios David , Auclair Marie-Christine , Kim Kelly , Bourrier Lise , Dawson Lauren , DaSilva Kamary Coriolano , Marples Pamela , Watts Rick , Thull-Freedman Jennifer , McGrath Patrick , Graham Timothy A. D. , Hartling Lisa , Erickson Tannis , Foot Brendon , Schreiner Kurt , Leung Julie ,   the KidsCAN PERC Innovative Pediatric Clinical Trials Methods Core, Offringa Martin , Pechlivanoglou Petros , Pullenayegum Eleanor , Rios Juan David , Round Jeff 
Published: March 2021

Abstract
Background
Patients and their families often have preferences for medical care that relate to wider considerations beyond the clinical effectiveness of the proposed interventions. Traditionally, these preferences have not been adequately considered in research. Research questions where patients and families have strong preferences may not be appropriate for traditional randomized controlled trials (RCTs) due to threats to internal and external validity, as there may be high levels of drop-out and non-adherence or recruitment of a sample that is not representative of the treatment population. Several preference-informed designs have been developed to address problems with traditional RCTs, but these designs have their own limitations and may not be suitable for many research questions where strong preferences and opinions are present.

Methods
In this paper, we propose a novel and innovative preference-informed complementary trial (PICT) design which addresses key weaknesses with both traditional RCTs and available preference-informed designs. In the PICT design, complementary trials would be operated within a single study, and patients and/or families would be given the opportunity to choose between a trial with all treatment options available and a trial with treatment options that exclude the option which is subject to strong preferences. This approach would allow those with strong preferences to take part in research and would improve external validity through recruiting more representative populations and internal validity. Here we discuss the strengths and limitations of the PICT design and considerations for analysis and present a motivating example for the design based on the use of opioids for pain management for children with musculoskeletal injuries.

Conclusions
PICTs provide a novel and innovative design for clinical trials with more than two arms, which can address problems with existing preference-informed trial designs and enhance the ability of researchers to reflect shared decision-making in research as well as improving the validity of trials of topics with strong preferences.
The effect of opioid-free anesthesia on the quality of recovery after gynecological laparoscopy: study protocol for a prospective randomized controlled trial
Authors: Song Jae Yen , Choi Hoon , Chae Minsuk , Ko Jemin , Moon Young Eun 
Published: March 2021

AbstractBackgroundBecause of the indiscriminate use of opioids during the perioperative period, opioid-free anesthesia (OFA) has been increasingly required. Nevertheless, the studies on the detailed techniques and effects of OFA are not sufficient. The Quality of Recovery-40 (QoR-40) questionnaire is a validated assessment tool for measuring recovery from general anesthesia. However, no study has used the QoR-40 to determine if OFA leads to better recovery than standard general anesthesia. Therefore, we aim to perform this study to determine the effects of OFA using dexmedetomidine and lidocaine on the quality of recovery as well as the various postoperative outcomes.MethodsThe participants (n = 78) will be allocated to one of the two groups; the study group will receive bolus and infusion of dexmedetomidine and lidocaine, and the control group will receive remifentanil infusion during general anesthesia for gynecological laparoscopy. The other processes including anesthetic and postoperative care will be performed similarly in the two groups. Intraoperative hemodynamic, anesthetic, and nociceptive variables will be recorded. Postoperative outcomes such as QoR-40, pain severity, and opioid-related side effects will be assessed. Additionally, an ancillary cytokine study (inflammatory cytokine, stress hormone, and reactive oxygen species) will be performed during the study period.DiscussionThis will be the first study to determine the effect of OFA, using the combination of dexmedetomidine and lidocaine, on the quality of recovery after gynecological laparoscopy compared with standard general anesthesia using remifentanil. The findings from this study will provide scientific and clinical evidence on the efficacy of OFA.Trial registrationClinicalTrials.govNCT04409964. Registered on 28 May 2020
Some remarks on the sparse dominations for commutators of multi(sub)linear operator
Authors: Wang Zhidan 
Published: March 2021

AbstractWe establish pointwise sparse dominations for the iterated commutators of multi(sub)linear operators satisfying the$W_{q}$Wqcondition. As consequences, we present some quantitative weighted estimates for the commutators. In addition, we also obtain the Fefferman–Stein inequality, the Coifman–Fefferman inequality, and the local decay estimates regarding the iterated commutators.
Bupivacaine inhibits a small conductance calcium‐activated potassium type 2 channel in human embryonic kidney 293 cells
Authors: Chen Hongfei , Jin Zhousheng , Xia Fangfang , Fu Zhijian 
Published: March 2021

Abstract
Background
Bupivacaine blocks many ion channels in the heart muscle, causing severe cardiotoxicity. Small-conductance calcium-activated potassium type 2 channels (SK2 channels) are widely distributed in the heart cells and are involved in relevant physiological functions. However, whether bupivacaine can inhibit SK2 channels is still unclear. This study investigated the effect of bupivacaine on SK2 channels.

Methods
The SK2 channel gene was transfected into human embryonic kidney 293 cells (HEK-293 cells) with Lipofectamine 2000. The whole-cell patch-clamp technique was used to examine the effect of bupivacaine on SK2 channels. The concentration–response relationship of bupivacaine for inhibiting SK2 currents (0 mV) was fitted to a Hill equation, and the half-maximal inhibitory concentration (IC50) value was determined.

Results
Bupivacaine inhibited the SK2 channels reversibly in a dose-dependent manner. The IC50 value of bupivacaine, ropivacaine, and lidocaine on SK2 currents was 16.5, 46.5, and 77.8µM, respectively. The degree of SK2 current inhibition by bupivacaine depended on the intracellular concentration of free calcium.

Conclusions
The results of this study suggested the inhibitory effect of bupivacaine on SK2 channels. Future studies should explore the effects of SK2 on bupivacaine cardiotoxicity.
Association between physical restraint requirement and unfavorable neurologic outcomes in subarachnoid hemorrhage
Authors: Akiyama Kyoko , Inoue Akihiko , Hifumi Toru , Nakamura Kentaro , Taira Takuya , Nakagawa Shun , Jinno Keisuke , Manabe Arisa , Kinugasa Sayaka , Matsumura Hikaru , Shishido Hajime , Yokoyama Shota , Okazaki Tomoya , Hamaya Hideyuki , Takano Koshiro , Kiridume Kazutaka , Shinohara Natsuyo , Kawakita Kenya , Kuroda Yasuhiro 
Published: March 2021

Abstract
Background
Physical restraint has been commonly indicated to patients with brain dysfunction in neurocritical care. The effect of physical restraints on outcomes of critically ill adults remains controversial as no randomized controlled trials have compared its safety and efficacy, and the association between physical restraint requirement and neurological outcome in patients with subarachnoid hemorrhage (SAH) has not been fully examined. The aim of this study was to examine the association between physical restraint requirement and neurological outcomes in patients with SAH.

Methods
A single-center, retrospective study was conducted on patients with acute phase SAH treated for > 72 h in the intensive care unit from 2014 to 2020. Patients were divided into three groups based on the amount of time required for physical restraint during the first 24–72 h after admission: no, intermittent, and continuous use of physical restraint. Unfavorable neurologic outcome, assessed using the modified Rankin scale upon hospital discharge, has been considered as primary end point.

Results
Overall, 101 patients were included in the study, with 52 patients (51.5%) having unfavorable neurological outcomes. Among them, 46 patients (45.5%) did not use physical restraint, and 55 (54.5%) patients used physical restraint during the first 24–72 h after admission: 26 (25.7%) intermittent and 29 (28.7%) continuous. Multivariable logistic regression analysis showed that continuous use of physical restraint during the first 24–72 h after admission was significantly associated with unfavorable neurological outcomes in patients with SAH (odds ratio, 3.54; 95% confidence interval, 1.05–13.06; p = 0.042) compared with no physical restraint.

Conclusions
Continuous use of physical restraint during the first 24–72 h after admission was more significantly associated with unfavorable neurological outcomes than no physical restraint among patients with SAH during the acute phase.
Self-reported infertility diagnoses and treatment history approximately 20 years after fertility treatment initiation
Authors: Jung Alesia M. , Missmer Stacey A. , Cramer Daniel W. , Ginsburg Elizabeth S. , Terry Kathryn L. , Vitonis Allison F. , Farland Leslie V. 
Published: March 2021

Abstract
Background
Infertility history may have important implications for clinical practice and scientific discovery. Previous research on the validity of self-reported infertility measurements has been limited in scope and duration (< 5 years). In this study, we validated self-reported infertility history measures 15–23 years after fertility treatment initiation among women who utilized assisted reproductive technology (ART).

Methods
Women who received ART treatments from three Boston infertility clinics and who enrolled in a prior study (1994–2003) were re-contacted in 2018 for the AfteR Treatment Follow-up Study (ART-FS). Infertility history was collected from clinical records and two self-report questionnaires (at ART initiation and at ART-FS enrollment). Treatment history included specific details (fresh or frozen embryo transfers, number of cycles) and treatment recall prior to ART initiation. Self-reported infertility diagnoses included polycystic ovary syndrome (PCOS), endometriosis, uterine factor infertility, tubal factor infertility, diminished ovarian reserve/advanced maternal age, male factor infertility, and other/unknown. We compared self-reported measures from 2018 to self-reported and clinical data from prior study initiation, using Cohen’s kappa, sensitivity, specificity, and 95% confidence intervals.

Results
Of 2644 women we attempted to recontact, 808 completed the ART-FS, with an average follow-up of 19.6 years (standard deviation: 2.7). Recall of fertility treatment usage had moderate sensitivity (IVF = 0.85, Clomiphene/Gonadotropin = 0.81) but low specificity across different infertility treatment modalities (IVF = 0.63, Clomiphene/Gonadotropin = 0.55). Specific IVF details had low to moderate validity and reliability with clinical records. Reliability of recalled infertility diagnosis was higher when compared to self-report at ART initiation (PCOS K = 0.66, Endometriosis K = 0.76, Tubal K = 0.73) than when compared to clinical records (PCOS K = 0.31, Endometriosis K = 0.48, Tubal K = 0.62) and varied by diagnosis.

Conclusions
The ability of women to recall specific IVF treatment details was moderately accurate and recall of self-reported infertility diagnosis varied by diagnosis and measurement method.
Military medical research on internal diseases in modern warfare: new concepts, demands, challenges, and opportunities
Authors: Liu Guang-Dong , Wang Nan , Wang Hai-Ming , Li Xin , Shao Jun-Jie , Liu Zi-Fan , Jiang Min , Wang Lin , Wang Zi-Kai , Li Meng , Cao Xue-Ying , Wang Jiang , Zhang Ran , Chen Yun-Dai 
Published: March 2021

AbstractBattlefield internal medicine aims at the treatment of combatants and noncombatants with various internal diseases on the battlefield. The military medical research on battlefield internal diseases focuses on the pathogenesis, clinical management, and prevention of internal diseases under military war conditions. In both wartime and peacetime, the soldiers suffer from more internal diseases than surgical wounds. With the introduction of high-tech weapons, including chemical, physical, and biological agents, a large number of special internal illnesses and casualties will appear in future wars. The battles often occur in special environments, such as high or low temperatures, plateau or polar areas, and micro- or hyper-gravity. The current theories of battlefield internal medicine are mainly derived from wars decades ago and cannot meet the needs of military medical support under the conditions of modern warfare. Therefore, the military medical research on battlefield internal medicine should be based on contemporary military situations, focus on the purpose of treating battlefield internal diseases, and adhere to the actual needs of the troops in peacetime and wartime. We should investigate the pathogenesis of battlefield internal diseases and explore the threats that may arise in future wars to ensure the advancement of battlefield internal medicine. This review highlights new concepts, demands, challenges, and opportunities for the further development of military medical research on battlefield internal medicine.
Dichloroacetate as a possible treatment for endometriosis-associated pain: a single-arm open-label exploratory clinical trial (EPiC)
Authors: Leow H. W. , Koscielniak M. , Williams L. , Saunders P. T. K. , Daniels J. , Doust A. M. , Jones M-C , Ferguson G. D. , Bagger Y. , Horne A. W. , Whitaker L. H. R. 
Published: March 2021

Abstract
Background
Endometriosis (where endometrial-like tissue is found outside the uterus) affects ~ 176 million women worldwide and can lead to debilitating pelvic pain. There is an unmet need for new medical treatment options for endometriosis. Pelvic peritoneal mesothelial cells of women with endometriosis exhibit detrimental metabolic reprogramming that creates an environment favouring the formation and survival of endometriosis lesions. We have generated powerful preclinical proof-of-concept data to show that it is possible to correct this metabolic phenotype using dichloroacetate (DCA), a non-hormonal compound previously used to treat rare metabolic disorders in children. We plan a single-arm, open-label, single site exploratory clinical trial to inform the design of a future randomised controlled trial (RCT) to determine the efficacy of DCA for the treatment of endometriosis-associated pain.

Methods
We will recruit 30 women with endometriosis-associated pain over a 6-month period. All participants will receive approximately 6.25 mg/kg oral DCA capsules twice daily for 6 weeks, with a dose increase to approximately 12.5 mg/kg twice daily for a further 6 weeks if their pain has not been adequately controlled on this dose regime and side-effects are acceptable. If pain is adequately controlled with minimal side-effects, the lower dose will be continued for a further 6 weeks. The primary objective is to determine whether it is possible to achieve acceptable recruitment and retention rates within the defined exclusion and inclusion criteria. Secondary objectives are to determine the acceptability of the trial to participants, including the proposed methods of recruitment, treatment, follow-up frequency and number of questionnaires. The recruitment rate will be determined by the proportion of patients recruited from the pool of eligible women. The retention rate will be determined by the proportion of participants who attended the final trial visit.

Discussion
This is a feasibility study to explore effectiveness and acceptability of the proposed field methodology (recruitment, retention, study processes and compliance with treatment). The results will be used to inform the design of a future RCT.

Trial registration
ClinicalTrials.gov, NCT04046081 Registered 6 August 2019
Visual search under physical effort is faster but more vulnerable to distractor interference
Authors: Park Hyung-Bum , Ahn Shinhae , Zhang Weiwei 
Published: March 2021

AbstractCognition and action are often intertwined in everyday life. It is thus pivotal to understand how cognitive processes operate with concurrent actions. The present study aims to assess how simple physical effort operationalized as isometric muscle contractions affects visual attention and inhibitory control. In a dual-task paradigm, participants performed a singleton search task and a handgrip task concurrently. In the search task, the target was a shape singleton among distractors with a homogeneous but different shape. A salient-but-irrelevant distractor with a unique color (i.e., color singleton) appeared on half of the trials (Singleton distractor presentcondition), and its presence often captures spatial attention. Critically, the visual search task was performed by the participants with concurrent hand grip exertion, at 5% or 40% of their maximum strength (low vs. high physical load), on a hand dynamometer. We found that visual search under physical effort is faster, but more vulnerable to distractor interference, potentially due to arousal and reduced inhibitory control, respectively. The two effects further manifest in different aspects of RT distributions that can be captured by different components of the ex-Gaussian model using hierarchical Bayesian method. Together, these results provide behavioral evidence and a novel model for two dissociable cognitive mechanisms underlying the effects of simple muscle exertion on the ongoing visual search process on a moment-by-moment basis.
Categorized wetland preference and life forms of the vascular plants in the Korean Peninsula
Authors: Choung Yeonsook , Min Byeong Mee , Lee Kyu Song , Cho Kang-Hyun , Joo Kwang Yeong , Hyun Jin-Oh , Na Hye Ryun , Oh Hyun Kyung , Nam Gi-Heum , Kim Jin-Seok , Cho Soyeon , Lee Jongsung , Jung Sangyeop , Lee Jaeyeon 
Published: March 2021

Abstract
Background
In 2020, a categorized list of wetland preferences, major habitats, and life forms of 4145 vascular plant taxa occurring in the Korean Peninsula was published by the National Institute of Biological Resources. We analyzed the list and explored the distribution patterns of the five categorized groups according to wetland preference, along with the information on the major habitats and the life forms of the plants belonging to those categories.

Results
Out of 4145 taxa, we found that 729 wetland plant taxa (18%) occur in Korea: 401 obligate wetland plants and 328 facultative wetland plants. Among the 729 wetland taxa, the majority (73%) was hygrophytes and the remaining 27% was aquatic macrophytes. Furthermore, almost all of the wetland taxa are herbs; so, woody plants are only 4.7%. The 16 carnivorous taxa distributed in Korea were characterized as obligate wetland plants.

Conclusions
We expect the categorized information would promote understanding of the characteristics of the plant species and would be an important source for understanding, conservation, and restoration of wetland ecosystems.
Potential of some endophytic bacteria in biological control of root-knot nematode Meloidogyne incognita
Authors: Moslehi Shalaleh , Pourmehr Salar , Shirzad Akbar , Khakvar Reza 
Published: March 2021

Abstract
Background
Root-knot nematodes (Meloidogyne spp.) are among the most important plant pathogens. Biological control is one of the safety and effective methods for control of these nematodes. The aim of the present study was the isolation and identification of endophytic bacteria from tomato fields in some areas of Iran in order to evaluate their biocontrol potential against root-knot nematode. In the present study, the population of Meloidogyne was collected from infected cucumber roots of a greenhouse, and the bacteria were isolated from tomato samples collected from the fields in West-Azarbaijan province of Iran. The effects of the bacterial isolates on hatching and mortality of nematode second-stage juveniles were evaluated, and the effects of six selected isolates on infection of a susceptible cultivar of tomato with nematode were evaluated under greenhouse conditions.

Results
The root-knot nematode was identified as Meloidogyne incognita. Results showed that the all isolates exhibited considerable inhibitory effects on nematode hatching. The bacterial isolates also caused the mortality of juveniles. Six bacterial isolates with notable biocontrol potential were selected, and supplementary experiments and molecular identification of selected bacterial isolates were performed. Isolates 1, 2, 5, 7, 10, and 11 were identified as follows: Bacillus wiedmannii (MW405861), Pseudoxantomonas mexicana (MW405860), Pseudomonas thivervalensis (MW405862), Serratia liquefaciens (MW405864), Pseudomonas chlororaphis (MW405863), and P. fluorescens (MW405825), respectively. Based on the results of the greenhouse experiment, the selected isolates exhibited good results in terms of reduction of galls and egg masses of nematode. However, B. wiedmannii and S. liquefaciens had the best results in reduction of all investigated factors compared to other isolates. P. mexicana, P. chlororaphis, and P. fluorescens resulted moderate effects. P. thivervalensis was less effective than the others and in some cases had no effect on nematode reduction.

Conclusions
The results showed that endophytic bacteria are good candidates for management of root-knot nematodes. The use of such agents instead of chemicals will be very valuable to the control of nematodes.
Comparison of postoperative analgesic effects of two doses of dexamethasone in ultrasound-guided transversus abdominis plane block for inguinal hernia repair: a randomized controlled trial
Authors: Abdel-wahab Amani H. , Osman Ekram A. , Ahmed Abubakr Y. 
Published: March 2021

Abstract
Background
Ninety patients American Society of Anesthesiologists (ASA) I–II, aged (18–60 years), were enrolled in this randomized controlled trial. All enrolled patients had undergone elective primary unilateral open inguinal hernia repair under spinal anesthesia; at the end of the surgery, transversus abdominis plane (TAP) block was done by bupivacaine combined with 4 mg dexamethasone in (group I), 8 mg dexamethasone in (group II), or saline in (group III.). We aimed to compare the analgesic efficacy of two different doses of dexamethasone (4 mg and 8 mg) added to bupivacaine in a unilateral single-injection (TAP) block. The first outcome measure was the time of the first analgesic request, and the secondary outcome measure was the VAS scale in the first postoperative 24 h.

Results
There was no need for any analgesia in group I and group II in the first postoperative 24 h. The time of the first analgesic request in group III was 720 ± 90 min. VAS scores were significantly lower in group I and group II than in group III, with no significant difference between group I and group II.

Conclusions
There is no difference in the first postoperative 24 h analgesic effect of the two doses of dexamethasone when added to a long-acting local anesthetic mixture in TAP blocks in patients undergoing inguinal hernia repair.

Trial registration
ClinicalTrials.gov, NCT03863977