bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Ambivalent Sexism on Intimate Partner Violence Tolerance and Mental Violence in a Chinese Female Sample: Relationship Causality Orientation as a Moderator
Authors: Yang Chunhui , Liu Wanlan , Wang Yihuan , Xu Shuang , Xu Yuxi , Yang Lujia , Zhou Qi , Li Junyi
Published: November 2022

The current study examined how the general tolerance of women's intimate partner violence and mental violence perpetration are affected by women's ambivalent sexism and relationship causality orientation. One hundred and forty-nine of 221 Chinese female participants recruited on an online platform were included in the final data analysis. The results showed that causality orientation plays a moderating role. Specifically, as controlled orientation increased, the relationship between hostile sexism and intimate partner violence tolerance became stronger. As the autonomous orientation increased, the relationship between benevolent sexism and intimate partner violence tolerance became weaker. Hostile sexism and controlled orientation positively predict women's mental violence perpetration.
Ethical challenges in clinical studies with adaptive design in oncology
Authors: Paul Norbert W. , Mahdiani Hamideh
Published: November 2022

Novel immune therapies are increasingly based on the molecular differentiation of disease patterns. The related clinical studies are thus more often characterized by the so-called adaptive study designs (umbrella or basket studies including platform studies), which are continuously adjusted based on novel results. This paper analyses new study designs beyond the often-postulated need for regulation in order to identify ethical problems based on typical structural features and to—whenever possible—suggest solutions. To do so, it addresses the following topics: the relationship between social and scientific values of a study as well as aspects of the scientific validity of new forms of evidence; the inclusion of study subjects under the condition of relative uncertainty; specific challenges in the process of ethical approval, and ethical and practical challenges in the process of informing patients and receiving informed consent. Additionally, the topic of a potential risk–benefit assessment of such therapies is addressed.
Implementation of Acupuncture in Routine Oncology Care: A Comparison of Physicians’, Nurses’, Physiotherapists’ and Acupuncturists’ Practice and Beliefs
Authors: Efverman Anna
Published: November 2022

Background:

It is important to investigate beliefs in acupuncture in professionals because professionals’ expectations may affect treatment outcomes.

Aim:

To document the type, number, and education of professionals practicing acupuncture. Further, to compare beliefs about the effectiveness of acupuncture for common cancer related symptoms in the different types of professionals.

Methods:

This cross-sectional study employed a questionnaire on practice and beliefs regarding acupuncture effects for symptoms that commonly occur in patients treated within oncology care settings. The respondents (n = 555) consisted of oncology professionals that is, physicians (n = 133), nurses (n = 172), and physiotherapists (n = 117). Additional respondents consisted of acupuncturists (n = 133), working outside approved health care.

Results:

Of the respondents, acupuncture was practiced by 4% of the physicians, 6% of the nurses, 58% of the physiotherapists, and 90% of the acupuncturists. The professionals believed acupuncture to be effective for pain (of the physicians, nurses, physiotherapists, and acupuncturists, 94%, 98%, 89%, and 99% respectively believed in the effectiveness), chemotherapy-induced nausea (corresponding figures: 74%, 89%, 89%, and 93%), and vasomotor symptoms (corresponding figures: 71%, 81%, 80%, and 97%). The physicians believed acupuncture to be effective in a mean of 5 symptoms, nurses in 6 symptoms, physiotherapists in 6 symptoms, and acupuncturists in 10 symptoms ( P < .001).

Conclusions:

Since the professionals varied substantially regarding practice, education and beliefs in acupuncture, oncology clinics may consider delivering patient preferred acupuncture according to evidence-informed guidelines rather than on varying preferences among the professionals, since professionals’ treatment expectations may modify treatment outcomes.
Topology and redescriptions detect multiple alternative biological pathways from clinical phenotypes
Authors: Karisani Negin , Platt Daniel E , Basu Saugata , Parida Laxmi
Published: November 2022

Biological pathways play a crucial role in the properties of diseases and are important in drug discovery. Identifying the logical relationships among distinctive phenotypic clusters could reveal possible connections to the underlying pathways. However, this process is challenging since clinical phenotypes are often available through unstructured electronic health records. Moreover, in the absence of a standardized questionnaire, there could be bias among physicians toward selecting certain medical terms. In this article, we develop an efficient pipeline to address these challenges and help practitioners to reveal the pathways associated with the disease. We use topological data analysis and redescriptions and propose a pipeline of four phases: (1) pre-processing the clinical notes to extract the salient concepts, (2) constructing a feature space of the patients to characterize the extracted concepts, (3) leveraging the topological properties to distill the available knowledge and visualize the extracted features, and finally, (4) investigating the bias in the clinical notes of the selected features and identify possible pathways. Our experiments on a publicly available dataset of COVID-19 clinical notes testify that our pipeline can indeed extract meaningful pathways.
Conducting Implementation Research in Stroke Rehabilitation: A Case Example and Considerations for Study Design
Authors: Juckett Lisa A. , Wengerd Lauren R. , Banhos Meredith , Darragh Amy R.
Published: November 2022

As neurorehabilitation research continues to grow, the field must ensure its scientific discoveries are implemented into routine clinical care. Without targeted efforts to increase the implementation of evidence into practice, patients may never see the benefits of interventions, assessments, and technologies developed in the confines of empirical studies. This article serves as a response to Lynch et al’s 2018 Point of View piece in Neurorehabilitation and Neural Repair that underscored the urgent need for implementation studies to expedite the application of neurorehabilitation evidence in practice. To address this need, we provide the following 4 considerations investigators should contemplate when designing their own studies at the intersection of implementation and neurorehabilitation research: (a) consideration of guiding theories, models, and frameworks, (b) consideration of implementation strategies, (c) considerations of target outcomes, and (d) consideration of hybrid effectiveness-implementation designs. To conclude, we also provide a study exemplar to depict how these considerations can be integrated into the neurorehabilitation research field to narrow the evidence-to-practice gap.
Modeling optimal patient transport in a stroke network capable of remote telerobotic endovascular therapy
Authors: Beaman Charles , Holodinsky Jessalyn K , Goyal Mayank , Tateshima Satoshi , Hill Michael D , Saver Jeffrey L , Kamal Noreen
Published: November 2022

Background

Telerobotic endovascular therapy (EVT) has the potential to decrease time to treatment and expand existing networks of care to more rural populations. It is currently unclear how its implementation would impact existing stroke networks.

Methods

Conditional probability models were generated to predict the probability of excellent outcome for patients with suspected large vessel occlusion (LVO). A baseline stroke network was created for California using existing intravenous thrombolysis (IVT) centers and comprehensive stroke centers (CSCs) capable of IVT and EVT. Optimal transport decisions and catchment areas were generated for the baseline model and three hypothetical scenarios through conversion of IVT centers at various distances from a CSC into centers capable of telerobotic EVT [i.e., hospitals ≥15 and <50 miles from a CSC were converted (Scenario 1), ≥50 and <100 miles (Scenario 2), and ≥100 miles (Scenario 3)]. Procedural times and success rates were varied systematically.

Results

Telerobotic EVT centers decreased median travel time for LVO patients in all three scenarios. The estimated number of robotically treated LVOs per year in Scenarios 1, 2, and 3 were 2,172, 740, and 212, respectively. Scenario 1 (15–50 miles) was the most sensitive to robotic time delay and success rate, but all three scenarios were more sensitive to decreases in procedural success rate compared to time delay.

Conclusions

Telerobotic EVT has the potential to improve care for stroke patients outside of major urban centers. Compared to procedural time delays in robotic EVT, a decrease in procedural success rate would not be well tolerated.
Development of a rolling angle estimation algorithm to improve the performance of implement leveling-control systems for agricultural tractors
Authors: Yu Ji Hun , Park Jin Kam , Cheon Su Hwan , Byeon Seo Jung , Lee Jin Woong
Published: November 2022

Agricultural tractors are connected with various implements such as plow, baler, rotovator, and loader for performing agricultural work. In particular, the rotovator is used to crush and uniformly spread the soil after plowing operations. However, achieving uniformly spread soil and flattened fields using rotovator can be extremely challenging, because the soil is often pushed to a particular side or remains on a slope owing to the variations in soil composition, plowing depth, and the skill level of workers, which consequently affects the transplantation work. This study aims to analyze the prediction accuracy of the implement and tractor attitudes as a reference standard by (a) developing an algorithm to predict the implement attitude based on the hitch height, support points of the lower link and lift rod, and distance between the lower links, through four-section link mathematical modeling for a three-point hitch system, and (b) using an observer to predict the tractor attitude using a Kalman filter with gyroscopic and acceleration sensors. We developed a control algorithm using the gyroscopic and acceleration information from the sensor to improve the precision and adjustment speed of the conventional tractor–implement leveling-control system. In addition, the performance improvement was verified by comparing the conventional and proposed systems. The results revealed that the error rates in the proposed system were up to 72% less than those of the conventional system, implying that the control performance of the stated system could be improved by reducing the implement attitude estimation error and tractor attitude measurement delay.
The constructed quality of Israeli TV on Netflix: The cases of Fauda and Shtisel
Authors: Lavie Noa
Published: November 2022

This study investigates how the concept of ‘quality TV’ is evolving in the age of streaming video on demand (SVOD) platforms, using reviews of two Israeli TV series on Netflix – Fauda and Shtisel. In accordance with Pierre Bourdieu’s view of journalistic reviewers as social agents and intermediaries with the power to enshrine cultural artifacts in an artistic canon, the study is based on a qualitative analysis of reviews of these two series published on major Anglo-American journalistic platforms. The analysis shows how the reviewers take part in constructing the Netflix brand of ‘a ‘foreign-language quality TV’ series.
Content reporting and effectiveness of therapeutic exercise in the management of massive rotator cuff tears: A systematic review with 490 patients
Authors: Fernández-Matías Rubén , García-Pérez Fernando , Requejo-Salinas Néstor , Gavín-González Carlos , Martínez-Martín Javier , García-Valencia Homero , Flórez-García Mariano Tomás
Published: November 2022

Background

Massive rotator cuff tears (MRCT) account for a substantial fraction of tears above the age of 60 years. However, there are no clear criteria for prescription parameters within therapeutic exercise treatments. The aim of this study was to evaluate the effects and characteristics of therapeutic exercise treatments in patients with MRCT.

Methods

A systematic search was conducted in MEDLINE/PubMed, Web of Science, SPORTDiscus, SciELO, Scopus and EMBASE from inception to August 2022. Studies were included if they evaluated the effects of exercise on patients with MRCT. The risk of bias was evaluated and the Consensus on Exercise Reporting Template (CERT) was also used. A narrative synthesis without meta-analysis was performed.

Results

One randomized controlled trial, two non-randomized studies, six non-controlled studies, one case series and four retrospective studies were included. They ranged from serious to moderate risk of bias. The CERT reflected a poor description of the exercise programmes. Studies showed a pattern of improvements in most patient-reported outcome measures (PROM) surpassing the MCID, and active elevation range of motion.

Conclusions

There is limited evidence that exercise and co-interventions are effective in the management of some patients with MRCT, based on a systematic review without meta-analysis. Future research should improve content reporting.

Level of evidence

IV.
The Biden Doctrine and China's response
Authors: Kim Dongchan
Published: November 2022

The purpose of this paper is to explain how China is reacting to U.S. foreign policy under President Biden (“The Biden Doctrine”). Using official statements and documents, this paper establishes that “authoritarianism versus democracy” has become the organizing principle of the Biden Doctrine, and that principle is supported by three “pillars”—alliances, multilateralism, and strategic risk reduction. The Biden Doctrine is focused on strengthening alliances and building multilateral partnerships that can provide a competitive edge against China, while also pursuing strategic risk reduction measures to contain competition to non-military areas, even as the United States steps up support for Taiwan. The Biden Doctrine has not been well-received in China, where it is viewed as an attempt at containment, and China has responded with stronger diplomatic rhetoric, increased military activity around Taiwan, strengthened partnerships with U.S. adversaries, and (albeit strained) efforts to maintain good relations with Europe. The paper concludes that the interplay between U.S. and Chinese foreign policies is increasing the risk of a new type of Cold War, especially over geographical flashpoints like Taiwan.
Comparison of Surgical Wait Times and Procedure Length in the Management of Postaxial Polydactyly Using Local or General Anesthesia
Authors: Mosa Adam , Somasundaram Mithila , Ferdosi Diba Vahidi , Davidge Kristen , Clarke Howard M. , Ho Emily S. , Kwan-Wong Terence
Published: November 2022

Introduction: For infants with ulnar polydactyly, surgical removal of the supernumerary digit can be performed under general or local anesthetic. This study evaluated the wait times, surgical duration, and sedation times associated with performing the procedure under local versus general anesthetic in infants with ulnar polydactyly. Methods: The databases of three surgeons at our institution were reviewed for children less than 2 years of age who underwent surgery for non-syndromic ulnar polydactyly. Data collection included patient demographics, wait times, duration of surgery and sedation and complications. Results: The study included children (n  =  55) who received treatment under local (n  =  22) or general (n  =  33) anesthesia. The wait times for the local anesthetic group were significantly shorter than the general anesthetic group (p < 0.05) for: referral to first consultation appointment; referral to surgery date, and decision date to surgery date. The duration of surgery (17.9  ±  6.9 vs 36.6  ±  20.2 min) and sedation time (26.3  ±  11.1 vs 74.8  ±  29.1 min) were significantly shorter in the local anaesthetic group (p < 0.05). There were no differences in complication rates between the groups. Conclusion: In this single-institution retrospective analysis, treatment of non-syndromic ulnar polydactyly with local anesthetic and bottle sedation was associated with shorter wait times, and duration of surgery and sedation. Level of Evidence: III, retrospective chart review and quality improvement initiative
Examining the geometry of streets through accessibility: new insights from streetspace allocation analysis
Authors: Palominos Nicolas , Smith Duncan A
Published: November 2022

This paper describes streetspace allocation analysis, a method that uses street cross-sections to measure footway and carriageway widths and quantify a key parameter of street design citywide. The resulting network-based streetspace allocation metrics are employed on a proof-of-concept study of train station service areas in London, applying shortest-path analysis under a place and walking prioritisation approach. Overall, streetspace allocation statistics for London confirm the citywide predominance of space allocated for vehicular transport over pedestrian uses. A comparison of the current distribution and proposed re-allocation of streetspace on streets near stations allows for the investigation of the effects of streetspace enhancements, which tend to be beneficial in reducing pedestrian movement impedance and extending service areas. The methods presented here can offer valuable analytical capacity for developing new transit-oriented schemes and designing place-based streets that support sustainable transport and sustainable urban development.
INBONE Total Ankle System: Clinical and Radiographic Outcomes
Authors: Padley Michelle A. , Albert Andrew J. , Anderson John G. , Bohay Donald R. , Maskill John D. , McKearney Daniel A. , Phillips Alexander , Potter Ramsey S. , Kothari Parin D.
Published: November 2022

Category:

Ankle Arthritis

Introduction/Purpose:

Ankle arthroplasties have undergone several generations of development since their initial introduction. Newer technologies in design have offered prosthetics which were more mobile and closer in articulation to human ankle joints. This includes increased motion of the coronal and sagittal planes, as well as less wear-and-tear of the prosthesis. Currently, second generation ankle arthroplasties have only shown promising results intermediately, and there has been very little research looking into the long term results of these devices. The INBONE total ankle system is a relatively new addition to the market that specifically has not been well researched. This project is aimed to outline their morbidly and mortality, as well as compare the long term results to other commonly used implants with data available.

Methods:

The study will be a retrospective, single-site cohort of past patients who have undergone INBONE total arthroplasty by Drs. Anderson, Bohay and Maskill at Orthopaedic Associates of Michigan (OAM). Pre-op indications will be evaluated, as well as lengthy post-op periods including 2 week, 6 week, 8 week, 1 year, and 2+ years follow up scores. Charts will be reviewed for inclusion and exclusion criteria. This includes demographic information, operative information, complications, reoperations, radiographic outcomes, and post-operative satisfaction scores. These scores include functional characteristics of ankle arthritis patients including pain level, walking distances, gait stability, varus/valgus stress, dorsi/plantarflexion ankle motion arc, hindfoot stability, and ankle alignment (AOFAS Score Criteria).

Results:

Study still in progress, results pending.

Conclusion:

Study still in progress, results pending.
Evaluation of the Clinical-Radiographic Results of Patients Undergoing Arthroscopic Metatarsal- Phalangeal Arthrodesis of the Hallux
Authors: Padua Bruno J. , Gomes Rogério d. , Gomes Anderson H. , Magalhães João Murilo B. , Fonseca Wagner V.
Published: November 2022

Category:

Arthroscopy; Midfoot/Forefoot

Introduction/Purpose:

Hallux rigidus is a common pathological condition of the foot, responsible for a great functional limitation. Metatarsophalangeal arthrodesis is an excellent therapeutic alternative for advanced stages of the disease, usually performed using an open technique. Forefoot arthroscopy has been developed in the last decade, with progressive expansion of indications, bringing encouraging results. Our objective is present the clinical-radiographic results of patients undergoing arthroscopic metatarsophalangeal arthrodesis of the hallux, showing the technique and reporting complications.

Methods:

This study involves a series of 9 patients (10 feet), all with advanced hallux rigidus (Coughlin-Shurnas grades 3 and 4). All patients underwent an arthroscopic procedure through two dorsal portals with small-joint instruments. Outcomes were assessed using the AOFAS functional score and a visual analogue scale of pain. The radiographic parameters of interest were metatarsal-phalangeal angulation in the anteroposterior (pre- and postoperative) and lateral (post-operative) views, as well as ray shortening.

Results:

All patients evolved with consolidation in radiographic control at 6 weeks postoperatively and showed a marked improvement in functional scores. We observed a reduction in the metatarsophalangeal angle, without shortening of the radius and of the finger. No patient had transfer metatarsalgia or complaints of cosmetic problems.

Conclusion:

Arthroscopic metatarsophalangeal arthrodesis is a very relevant therapeutic option for managing advanced stages of hallux rigidus, with minimal aggression and providing excellent results, in addition to a low incidence of complications.
Hindfoot Motion Analysis by Subtalar Compensation and Ankle Osteoarthritis Stage using a 3D Multi- Segment Foot Model
Authors: Park Gil Young , Lee Dong-Oh , Kwon So Hyeon , Lee Dong Yeon , Yoon Youngsik
Published: November 2022

Category:

Hindfoot

Introduction/Purpose:

Biomechanics of the hindfoot in ankle osteoarthritis (OA) have not yet fully understood. We aimed to identify hindfoot motions by gait analysis using multi-segment foot model (MFM) according to the stage of ankle OA or hindfoot alignment determined by the presence of subtalar compensation.

Methods:

We retrospectively reviewed the medical records, simple radiographs, and gait MFM data from 54 ankles which admitted to our hospital for the treatment of advanced ankle OA. Spatiotemporal gait parameters and 3-dimensional motions of hindfoot segment were analyzed according to sex, age, body mass index, the Takakura classification, and the presence of subtalar compensation.

Results:

As a result, all spatiotemporal gait parameters showed no significant difference according to the presence of subtalar compensation and the stage of ankle OA. With regard to the relationship between hindfoot segmental motion and the stage of ankle OA, only normalized step width was significantly different from each other (p value=0.028). Average motion of hindfoot (decompensation versus compensation) showed no significant difference in sagittal and transverse plane. In coronal movement of hindfoot, there were collapsed curves in both groups, which had constant significant difference. In comparison of 3a, 3b, and 4 stages of Takakura, more advanced 3b stages of ankle OA had the smaller sagittal range of motion compared to 3a (p value=0.028). Coronal movement of hindfoot in Takakura 3a/3b/4 all showed relatively flat pattern.

Conclusion:

In conclusion, spatiotemporal parameters were not affected by the alignment state of the heel resulted from subtalar compensation. Sagittal range of hindfoot motion decreased in the advanced ankle OA. Coronal movement of subtalar joint in ankle OA, once it was disrupted, showed no change regardless of the stage of ankle OA or compensation state of the hindfoot.
Clinical Profile of Physiotherapy Ambulatory Patients Adult Ankle and Foot Trauma Orthopedics Brazil
Authors: Santos Aquiles S.
Published: November 2022

Category:

Other; Ankle; Ankle Arthritis; Arthroscopy; Basic Sciences/Biologics; Bunion; Diabetes; Hindfoot; Lesser Toes; Midfoot/Forefoot; Sports; Trauma

Introduction/Purpose:

From a trauma point of view, the number of severely injured polytrauma patients decreased in the first few weeks of isolation. However, the number of cases observed with complex ankle and foot injuries. As ankle ligament injuries among the most prevalent traumatic conditions in an emergency care setting. Depending on the degree of energy, ankle and foot position, direction of the sprain, bone quality and soft tissue envelope, this trauma can have different outcomes and diagnoses.

Methods:

This is a retrospective study that will be carried out from the analysis of medical records of patients treated in an outpatient orthopedic trauma to the ankle and foot at UNIFESP, in which the care will be performed by a physical therapist provided to patients from the Unified Health System (SUS).

Results:

In this verification of medical records, it was analyzed that the profile of the outpatient patient with a predominance of atraumatic injuries.

Conclusion:

Most patients seen at the outpatient clinic have as their main source of treatment and the profile of these patients is chronic.
Tarsometatarsal Joint Preparation using a Modified Dorsal Approach vs Standard Approach: A Cadaver Study
Authors: Shah Ashish , Murali Sudarsan , Littlefield Zachary , Young Sean M. , Patch David A. , Jacob Roshan , Luque-Sanchez Kevin S. , Reed Logan , Elphingstone Joseph
Published: November 2022

Category:

Midfoot/Forefoot

Introduction/Purpose:

Lisfranc injuries are a relatively common midfoot injury involving the tarsometatarsal (TMT) joint. Surgical fixation typically involves open reduction with internal fixation or primary arthrodesis of the joint(s). The standard surgical approach to the TMT joint involves two dorsal incisions however, a recent study has suggested the use of a modified single dorsal incision approach. The goal of this paper is to compare the total surface area of the joint that can be prepared for primary arthrodesis of the TMT using the standard vs modified single dorsal approach.

Methods:

Ten fresh frozen below-the-knee cadaver specimens were randomly assigned to receive either the standard or modified dorsal single incision operative approach to the TMT joint. Prior to initiating the study, specimens were inspected with fluoroscopic radiographs for preexisting pathology or prior surgical intervention. The joint surface was visualized and then underwent articular preparation as for a joint fusion. After adequate joint preparation, the TMT joint was disarticulated and the surface was photographed for image analysis. Using ImageJ, articular joint surface preparation areas were measured by two blinded reviewers. to assess the joint surface preparation and this was compared by surgical approach.

Results:

After ImageJ and Mann-Whitney U statistical analysis, there was no significant difference in the amount of joint prepared when comparing the standard versus modified dorsal approach for the first three TMT joints (p= 0.548, p=0.310, p= 0.548). The percentage of joint preparation utilizing the standard dorsal approach versus the modified dorsal approach for TMT joints one through three are as follows (percentages utilized are listed as the median value with its correlating range): First TMT- 67.6% (range 26%) by the standard approach versus 71.7% (range 9%) by the modified dorsal approach, second TMT- 67.9% (range 24%) versus 65.7% (range 12%), and third TMT- 65.9% (range 42%) versus 59.6% (range 24%). Table 1 summarizes our results between each operative approach.

Conclusion:

With our findings, we demonstrate that a modified single dorsal approach to the Lisfranc joint provided comparable joint preparation for primary arthrodesis as the standard dual incision approach. However, the modified dorsal approach may be beneficial in that it avoids creating a skin bridge which has potential for necrosis with the standard two incision approach. The authors believe the comparable joint preparation combined with its potential to alleviate soft tissue complications make the modified dorsal approach a viable surgical approach for a TMT arthrodesis.
The Role of Diet and Nutrition on Fracture Healing: A Systematic Review
Authors: Singh Priya K. , Vankara Ashish , O'Sullivan Lucy , Aiyer Amiethab A.
Published: November 2022

Category:

Other

Introduction/Purpose:

Not only is poor nutritional status common amongst the elderly, but its incidence is also high amongst orthopedic trauma patients as injuries, and fractures more specifically, cause hypermetabolic states. The purpose of this review was to perform the most comprehensive analysis of literature published within the last decade to determine the effect of nutritional status on fracture healing, as well as outlining the effects of specific herbal supplements, vitamins and minerals.

Methods:

Following PRISMA guidelines, PubMed, Embase and Web of Science databases were searched using variations of the terms nutrition and malnutrition along with vitamins, minerals and proteins as well as fractures and fracture healing. Two independent reviewers screened articles, graded evidence quality, and extracted data. A total of 31 studies were related to nutritional status - 22 human studies and 9 animal studies - and 45 studies were related to specific herbs or food products - 2 human studies, 36 animal studies, and 7 review articles.

Results:

There is substantial variability in the definitions of nutritional status, with some quantitative measures including serum albumin and lymphocyte count being the most popular, and questionnaires like the Mini Nutritional Assessment (MNA) and the Malnutrition Universal Screening Tool (MUST). Published human studies predominately studied the effects of nutrition on traumatic fractures in the elderly or bone healing after spinal surgery. Consistently, hypoalbuminemia was found to be an independent risk factor of post-operative complications and longer hospital stays. Few studies reported on nutritional supplementation, but those that did found supplementation to be associated with lower rates of postoperative complications and wound infection, as well as shorter hospital stays. Although there is much evidence published on herbal supplements and food products in animals, there is a dearth of evidence of their benefits to humans with only two RCTs included in this analysis (demonstrating the benefits of Momiai and lactobacillus casei Shirota).

Conclusion:

Nutrition remains an easily targetable factor that can significantly improve fracture healing, especially amongst elderly populations. Although proper adherence to supplementation is rare, when attained its benefits are profound. To demonstrate that the beneficial effects of herbal supplements and food products on fracture healing seen in animal models persist in humans, future placebo-controlled trials are needed.
Host metabolome predicts the severity and onset of acute toxicities induced by CAR T-cell therapy
Authors: Jalota Akansha , Hershberger Courtney E. , Patel Manishkumar S. , Mian Agrima , Faruqi Aiman , Khademi Gholamreza , Rotroff Daniel M. , Hill Brian T. , Gupta Neetu
Published: November 2022

Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a highly effective treatment option for patients with relapsed/refractory large B-cell lymphoma. However, widespread use is deterred by the development of clinically significant acute inflammatory toxicities, including cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), that induce significant morbidity and require close monitoring. Identification of host biochemical signatures that predict the severity and time-to-onset of CRS and ICANS may assist patient stratification to enable timely mitigation strategies. Here, we report pretreatment host metabolites that are associated with CRS and ICANS induced by axicabtagene ciloleucel or tisagenlecleucel therapy. Both untargeted metabolomics analysis and validation using targeted assays revealed a significant association between the abundance of specific pretreatment biochemical entities and an increased risk and/or onset of clinically significant CRS (q < .1) and ICANS (q < .25). Higher pretreatment levels of plasma glucose and lower levels of cholesterol and glutamate were associated with a faster onset of CRS. In contrast, low baseline levels of the amino acids proline and glycine and the secondary bile acid isoursodeoxycholate were significantly correlated with clinically significant CRS. Lower concentration of the amino acid hydroxyproline was associated with higher grade and faster onset of ICANS, whereas low glutamine was negatively correlated with faster development of ICANS. Overall, our data indicate that the pretreatment host metabolome has biomarker potential in determining the risk of clinically significant CRS and ICANS, and may be useful in risk stratification of patients before anti-CD19 CAR T-cell therapy.
Predictors of survival in patients with MALT lymphoma: a retrospective, case-control study
Authors: Qi Shunan , Liu Xin , Noy Ariela , Lee Jisun , Teckie Sewit , Hajj Carla , Joffe Erel , Imber Brandon S. , Yahalom Joachim
Published: November 2022

There is limited understanding of the extent to which mucosa-associated lymphoid tissue (MALT) lymphoma affects a patient’s risk of death and how classically considered prognostic factors affect lymphoma-specific vs other noncancer mortality. This study analyzed major long-term outcomes of patients with MALT lymphoma and the prognostic significance of baseline clinical features. We reviewed the clinical features, treatments, disease course, and survival of 593 patients with MALT lymphoma diagnosed at Memorial Sloan Kettering between 2000 to 2012. Outcomes were analyzed using crude overall survival (OS) and relative survival (RS) by standardized mortality ratio. The median age was 60 years, 72% were at stage I/II. With a median follow-up of 9.2 years, the 10-year OS, lymphoma-specific mortality, and competing nonlymphoma mortality was 75%, 4%, and 21%, respectively; the overall standardized mortality ratio was 1.41 (95% confidence interval, 1.19-1.67; P < .001). Using multivariate analysis, older age, advanced stage, and poor performance status were independently associated with inferior OS. Several subgroups had similar RS to the normal matched population, including those with an age of ≥70 years, stage I, and skin or gastric origin. Increased lymphoma-specific death was associated with spread disease, whereas death from nonlymphoma causes was correlated with older age. Overall, a diagnosis of MALT lymphoma was associated with moderately compromised survival. Age and advanced-stage disease emerged as the most important prognostic factors. Younger patients had better OS but worse RS. Disease dissemination was the lymphoma-specific risk factor.
Antileukemic properties of the kinase inhibitor OTSSP167 in T-cell acute lymphoblastic leukemia
Authors: Bridges Cory Seth , Chen Taylor J. , Puppi Monica , Rabin Karen R. , Lacorazza H. Daniel
Published: November 2022

Novel drugs are needed to increase treatment response in children with high-risk T-cell acute lymphoblastic leukemia (T-ALL). Following up on our previous report on the activation of the MAP2K7-JNK pathway in pediatric T-ALL, here we demonstrate that OTSSP167, recently shown to inhibit MAP2K7, has antileukemic capacity in T-ALL. OTSSP167 exhibited dose-dependent cytotoxicity against a panel of T-ALL cell lines with IC50 in the nanomolar range (10-50 nM). OTSSP167 induces apoptosis and cell cycle arrest in T-ALL cell lines, associated at least partially with the inhibition of MAP2K7 kinase activity and lower activation of its downstream substrate, JNK. Other leukemic T-cell survival pathways, such as mTOR and NOTCH1 were also inhibited. Daily intraperitoneal administration of 10 mg/kg OTSSP167 was well tolerated, with mice showing no hematological toxicity, and effective at reducing the expansion of human T-ALL cells in a cell-based xenograft model. The same dosage of OTSSP167 efficiently controlled the leukemia burden in the blood, bone marrow, and spleen of 3 patient-derived xenografts, which resulted in prolonged survival. OTSSP167 exhibited synergistic interactions when combined with dexamethasone, L-asparaginase, vincristine, and etoposide. Our findings reveal novel antileukemic properties of OTSSP167 in T-ALL and support the use of OTSSP167 as an adjuvant drug to increase treatment response and reduce relapses in pediatric T-ALL.
SIGIRR deficiency contributes to CD4 T cell abnormalities by facilitating the IL1/C/EBPβ/TNF-α signaling axis in rheumatoid arthritis
Authors: Teng Xiu , Mou Da-Chao , Li Hui-Fang , Jiao Ling , Wu Sha-Sha , Pi Jin-Kui , Wang Yan , Zhu Meng-Li , Tang Meng , Liu Yi
Published: November 2022

Background

Rheumatoid arthritis (RA) is a complex autoimmune disease with multiple etiological factors, among which aberrant memory CD4 T cells activation plays a key role in the initiation and perpetuation of the disease. SIGIRR (single immunoglobulin IL-1R-related receptor), a member of the IL-1 receptor (ILR) family, acts as a negative regulator of ILR and Toll-like receptor (TLR) downstream signaling pathways and inflammation. The aim of this study was to investigate the potential roles of SIGIRR on memory CD4 T cells in RA and the underlying cellular and molecular mechanisms.

Methods

Single-cell transcriptomics and bulk RNA sequencing data were integrated to predict SIGIRR gene distribution on different immune cell types of human PBMCs. Flow cytometry was employed to determine the differential expression of SIGIRR on memory CD4 T cells between the healthy and RA cohorts. A Spearman correlation study was used to determine the relationship between the percentage of SIGIRR+ memory CD4 T cells and RA disease activity. An AIA mouse model (antigen-induced arthritis) and CD4 T cells transfer experiments were performed to investigate the effect of SIGIRR deficiency on the development of arthritis in vivo. Overexpression of SIGIRR in memory CD4 T cells derived from human PBMCs or mouse spleens was utilized to confirm the roles of SIGIRR in the intracellular cytokine production of memory CD4 T cells. Immunoblots and RNA interference were employed to understand the molecular mechanism by which SIGIRR regulates TNF-α production in CD4 T cells.

Results

SIGIRR was preferentially distributed by human memory CD4 T cells, as revealed by single-cell RNA sequencing. SIGIRR expression was substantially reduced in RA patient-derived memory CD4 T cells, which was inversely associated with RA disease activity and related to enhanced TNF-α production. SIGIRR-deficient mice were more susceptible to antigen-induced arthritis (AIA), which was attributed to unleashed TNF-α production in memory CD4 T cells, confirmed by decreased TNF-α production resulting from ectopic expression of SIGIRR. Mechanistically, SIGIRR regulates the IL-1/C/EBPβ/TNF-α signaling axis, as established by experimental evidence and cis-acting factor bioinformatics analysis.

Conclusion

Taken together, SIGIRR deficiency in memory CD4 T cells in RA raises the possibility that receptor induction can target key abnormalities in T cells and represents a potentially novel strategy for immunomodulatory therapy.
Protein function annotation based on heterogeneous biological networks
Authors: Hu Sai , Luo Yingchun , Zhang Zhihong , Xiong Huijun , Yan Wei , Jiang Meiping , Zhao Bihai
Published: November 2022

Background

Accurate annotation of protein function is the key to understanding life at the molecular level and has great implications for biomedicine and pharmaceuticals. The rapid developments of high-throughput technologies have generated huge amounts of protein–protein interaction (PPI) data, which prompts the emergence of computational methods to determine protein function. Plagued by errors and noises hidden in PPI data, these computational methods have undertaken to focus on the prediction of functions by integrating the topology of protein interaction networks and multi-source biological data. Despite effective improvement of these computational methods, it is still challenging to build a suitable network model for integrating multiplex biological data.

Results

In this paper, we constructed a heterogeneous biological network by initially integrating original protein interaction networks, protein-domain association data and protein complexes. To prove the effectiveness of the heterogeneous biological network, we applied the propagation algorithm on this network, and proposed a novel iterative model, named Propagate on Heterogeneous Biological Networks (PHN) to score and rank functions in descending order from all functional partners, Finally, we picked out top L of these predicted functions as candidates to annotate the target protein. Our comprehensive experimental results demonstrated that PHN outperformed seven other competing approaches using cross-validation. Experimental results indicated that PHN performs significantly better than competing methods and improves the Area Under the Receiver-Operating Curve (AUROC) in Biological Process (BP), Molecular Function (MF) and Cellular Components (CC) by no less than 33%, 15% and 28%, respectively.

Conclusions

We demonstrated that integrating multi-source data into a heterogeneous biological network can preserve the complex relationship among multiplex biological data and improve the prediction accuracy of protein function by getting rid of the constraints of errors in PPI networks effectively. PHN, our proposed method, is effective for protein function prediction.
Using joint models to study the association between CD4 count and the risk of death in TB/HIV data
Authors: Mchunu Nobuhle N. , Mwambi Henry G. , Rizopoulos Dimitris , Reddy Tarylee , Yende-Zuma Nonhlanhla
Published: November 2022

Background

The association structure linking the longitudinal and survival sub-models is of fundamental importance in the joint modeling framework and the choice of this structure should be made based on the clinical background of the study. However, this information may not always be accessible and rationale for selecting this association structure has received relatively little attention in the literature. To this end, we aim to explore four alternative functional forms of the association structure between the CD4 count and the risk of death and provide rationale for selecting the optimal association structure for our data. We also aim to compare the results obtained from the joint model to those obtained from the time-varying Cox model.

Methods

We used data from the Centre for the AIDS Programme of Research in South Africa (CAPRISA) AIDS Treatment programme, the Starting Antiretroviral Therapy at Three Points in Tuberculosis (SAPiT) study, an open-label, three armed randomised, controlled trial between June 2005 and July 2010 (N=642). In our analysis, we combined the early and late integrated arms and compared results to the sequential arm. We utilized the Deviance Information Criterion (DIC) to select the final model with the best structure, with smaller values indicating better model adjustments to the data.

Results

Patient characteristics were similar across the study arms. Combined integrated therapy arms had a reduction of 55% in mortality (HR:0.45, 95% CI:0.28-0.72) compared to the sequential therapy arm. The joint model with a cumulative effects functional form was chosen as the best association structure. In particular, our joint model found that the area under the longitudinal profile of CD4 count was strongly associated with a 21% reduction in mortality (HR:0.79, 95% CI:0.72-0.86). Where as results from the time-varying Cox model showed a 19% reduction in mortality (HR:0.81, 95% CI:0.77-0.84).

Conclusions

In this paper we have shown that the “current value” association structure is not always the best structure that expresses the correct relationship between the outcomes in all settings, which is why it is crucial to explore alternative clinically meaningful association structures that links the longitudinal and survival processes.
A booster hepatitis B vaccine for children with maternal HBsAg positivity before 2 years of age could effectively prevent vaccine breakthrough infections
Authors: Song Yarong , Zhang Xin , Liu Minmin , Zhai Xiangjun , Liu Jianxun , Li Yi , Li Lili , Xiao Yiwei , Duan Zhongping , Jiang Jing , Ding Feng , Zhu Liguo , Jiang Jie , Zou Huaibin , Zhuang Hui , Wang Jie , Li Jie
Published: November 2022

Background

The long-term protective effect of hepatitis B vaccine (HepB), the incidence of hepatitis B virus (HBV) vaccine breakthrough infections (VBIs), and whether a booster HepB is necessary remain to be clarified in children born to mothers with chronic HBV infection.

Methods

Based on a long-term follow-up prospective cohort of 1177 hepatitis B surface antigen (HBsAg)-positive mothers and their paired infants which was established from 2009 to 2011, total 454 children with immunoprophylaxis success as determined by postvaccination serologic testing (PVST) at 7 months old were included in this study. Among the 454 children, 246 never had a booster HepB, and 208 children received a booster HepB from 1 to 5 years of age. Multivariate logistic regression analysis was used to analyse the risk factors for HBV VBIs.

Results

The hepatitis B surface antibody (anti-HBs) levels declined sharply from 7 months to 2 years old, and the anti-HBs seronegative rate in the children increased significantly from 2 years old. A total of 31 (6.83%) of the 454 children experienced VBIs, of which 7 had overt and 7 had occult HBV infections. Notably, 14 (45.16%) of the 31 children with VBIs were diagnosed at 2 years old, and all of them had anti-HBs positivity (> 10 mIU/mL) at 1 year old. Maternal hepatitis B e antigen (HBeAg) positivity, higher HBV DNA and HBsAg levels, lower initial infant anti-HBs levels and not receiving a booster HepB were independent risk factors for VBIs. The incidence of VBIs was significantly lower in children with a booster HepB than in nonboosted children (0.50 vs. 11.90%, P < 0.001), and none of the boosted children developed overt or occult HBV infection. The anti-HBs levels of 76.67% for the children with VBIs in the nonboosted group indicated positivity before VBIs was detected.

Conclusions

After the primary full immunization with HepB, children born to mothers with chronic HBV infection, especially the children with maternal HBeAg positivity, high HBV DNA levels, high HBsAg levels and/or low initial infant anti-HBs levels, were at a high risk of VBIs, and a booster HepB for these children before 2 years old, instead of when their anti-HBs level is < 10 mIU/mL, could reduce the incidence of VBIs.