bluuebunny/crossref_metadata_2025 huggingface dataset:
Rural Migration and Relative Deprivation in Agro-Pastoral Communities Under the Threat of Cattle Rustling in Nigeria
Authors: Sani Ibrahim Saifullahi , Ozdeser Huseyin , Cavusoglu Behiye , Abdullahi Shagali Aminu
Published: January 2021

Pastoral livestock production as a primary source of livelihood is increasingly becoming unsustainable due to the rapidly changing social context, perennial cattle rustling, unpredictable climatic conditions, and rapid population growth. Migration in response to these changes in social context has often increased competition for land and natural resources between the farmers and pastoralists. Using survey data from 1,750 agro-pastoral households, this study examines the impact of cattle rustling and relative deprivation on shaping the patterns of migration in Nigeria. The results of linear regression show that the loss of livestock, cattle rustling, income diversity, literacy, and herd size are significant determinants of migration patterns. These factors were instrumental in the households’ decision to migrate transitorily or permanently. While the findings indicate that relative deprivation is a significant push factor, migration in response to deprivation and cattle rustling may not necessarily decrease inequality due to weak social capital among the agro-pastoralists. In this sense, increasing pastoral social and economic capital is critical to the reduction of inequality and competition for natural capital. As such, rural livelihood enhancement intervention embedded within the context of a conflict mitigation mechanism is required to decrease the perceived relative deprivation.
Auricular Point Acupressure Smartphone Application to Manage Chronic Musculoskeletal Pain: A Longitudinal, One-Group, Open Pilot Trial
Authors: Kawi Jennifer , Yeh Chao Hsing , Li Mengchi , Caswell Keenan , Mazraani Maurice , Lukkahatai Nada , Mensah Sylvanus , Taylor Janiece , Budhathoki Chakra , Christo Paul
Published: January 2021

Background

Chronic musculoskeletal pain (CMP) is the most common self-reported chronic pain condition. Current treatment for CMP is limited.

Methods

This was a two-phase study. In Phase 1, three auricular point acupressure (APA)-naïve participants were recruited to explore their experiences of APA and a smartphone app was developed based on their feedback. In Phase 2, a prospective longitudinal study was used to examine the effectiveness of the smartphone app to self-manage CMP.

Results

Phase 1 resulted in the successful development of the APA smartphone app. In Phase 2, after four weeks of APA, participants reported reduced pain intensity (30%), pain interference (35%), and disability (40%), as well as improved physical function (47%). The mean score for the participants’ perception of treatment efficacy was 4.94 (SD = 2.08, scale of 0–7) indicating that approximately 70% of participants rated global improvements with noticeable changes. The majority (88%, n = 22) of the participants were satisfied with the treatment: 32% [8] were very satisfied and 56% [n = 14] were somewhat satisfied. The average frequency of pressing APA seeds per day was 2.93 times (SD = 2.27, range 0–10) and 1.60 minutes per time (SD = 2.64, range 0–10); the participants were able to adhere to the suggested pressing time per day, although they only pressed the ear points about 53% of the suggested time.

Conclusion

It is feasible for individuals to learn APA from the smartphone app and successfully self-administer APA to manage their pain. Participants found the app useful and were satisfied with the information provided through the app.
Toward Many Emerging Adulthoods: A Theory-Based Examination of the Features of Emerging Adulthood for Cross-Systems Youth
Authors: Bowen Elizabeth , Ball Annahita , Jones Annette Semanchin , Miller Berg
Published: January 2021

Although it is widely acknowledged that emerging adulthood is experienced differently by various groups, few studies have directly examined the theoretical features of emerging adulthood in vulnerable subpopulations of low-income young people in the United States. This study addressed this gap by exploring the salience of the five features proposed in emerging adulthood theory—identity exploration, instability, feeling in-between, sense of self-focus, and optimism for the future—for cross-systems youth. Two samples from prior qualitative studies of young people age 18–24 who had experienced homelessness, child welfare involvement, and/or educational disadvantage were combined for the analysis ( N = 50). We noted important divergences and nuances in the ways in which the theoretical features resonated with the sample. For example, most participants sought financial stability and independence, rather than identity and career exploration. The findings speak to the importance of further research to establish features of emerging adulthood in diverse populations.
Spine Surgery and Preoperative Hemoglobin, Hematocrit, and Hemoglobin A1c: A Systematic Review
Authors: Suresh Krishna V. , Wang Kevin , Sethi Ishaan , Zhang Bo , Margalit Adam , Puvanesarajah Varun , Jain Amit
Published: January 2021

Study Design:

Systematic review.

Objectives:

Synthesize previous studies evaluating clinical utility of preoperative Hb/Hct and HbA1c in patients undergoing common spinal procedures: anterior cervical discectomy and fusion (ACDF), posterior cervical fusion (PCF), posterior lumbar fusion (PLF), and lumbar decompression (LD).

Methods:

We queried PubMed, Embase, Cochrane Library, and Web of Science for literature on preoperative Hb/Hct and HbA1c and post-operative outcomes in adult patients undergoing ACDF, PCF, PLF, or LD surgeries.

Results:

Total of 4,307 publications were assessed. Twenty-one articles met inclusion criteria.

PCF and ACDF:

Decreased preoperative Hb/Hct were significant predictors of increased postoperative morbidity, including return to operating room, pulmonary complications, transfusions, and increased length of stay (LOS). For increased HbA1c, there was significant increase in risk of postoperative infection and cost of hospital stay.

PLF:

Decreased Hb/Hct was reported to be associated with increased risk of postoperative cardiac events, blood transfusion, and increased LOS. Elevated HbA1c was associated with increased risk of infection as well as higher visual analogue scores (VAS) and Oswestry disability index (ODI) scores.

LD:

LOS and total episode of care cost were increased in patients with preoperative HbA1c elevation.

Conclusion:

In adult patients undergoing spine surgery, preoperative Hb/Hct are clinically useful predictors for postoperative complications, transfusion rates, and LOS, and HbA1c is predictive for postoperative infection and functional outcomes. Using Hct values <35-38% and HbA1c >6.5%-6.9% for identifying patients at higher risk of postoperative complications is most supported by the literature. We recommend obtaining these labs as part of routine pre-operative risk stratification.

Level of Evidence:

III
Anatomical Parameters for Occipital Condyle Screws: An Analysis of 500 Condyles Using CT Scans
Authors: Bernstein David N. , Ikpeze Tochukwu C. , Foxx Kenneth , Omar Adan , Mesfin Addisu
Published: January 2021

Study Design:

Retrospective observational study.

Objective:

To establish occipital condyle dimensions (length, width, height), as well as the medialization angle necessary for safe occipital condyle screw placement in occipitocervical fixation.

Methods:

Between 1/2014-6/2014, patients who presented to a single level 1 academic trauma center emergency room and received computed tomography (CT) imaging of the cervical spine as part of routine clinical care were identified. After excluding patients with cervical fractures, neoplastic disease, or infection, 500 condyles representing 250 patients were analyzed. Condyle length, height, and width (all reported in millimeters [mm]) were evaluated on the sagittal, coronal, and axial series, respectively. Medialization angle (reported in degrees) was evaluated on the axial series of CT imaging. Measurements were compared by sex and age.

Results:

The average condyle length, width, and height were 18.6 millimeters (mm) (range, 14.5-23.0 mm), 10.5 mm (range, 7.4-13.8 mm), and 11.3 mm (7.1-15.3 mm), respectively. Additionally, the average occipital condyle medialization angle was 23° (range, 14-32°). Occipital condyles of men were significantly longer, wider, and taller (all comparisons, p < 0.05). The medialization angle was significantly steeper for women than men (p < 0.05). No measurement differences were appreciated by age.

Conclusion:

Our findings are similar to previous studies in the field; however, length appears slightly shorter. Further, measurement differences were appreciated by sex but not age. Thus, our measurement findings emphasize the importance of preoperative planning utilizing individual patient anatomy to ensure safe placement of occipital condyle screws for optimal outcomes.
Reoperation and Mortality Rates Following Elective 1 to 2 Level Lumbar Fusion: A Large State Database Analysis
Authors: Cummins Daniel , Hindoyan Kevork , Wu Hao-Hua , Theologis Alekos A. , Callahan Matthew , Tay Bobby , Berven Sigurd
Published: January 2021

Study Design:

Retrospective cohort.

Objective:

Reoperation to lumbar spinal fusion creates significant burden on patient quality of life and healthcare costs. We assessed rates, etiologies, and risk factors for reoperation following elective 1 to 2 level lumbar fusion.

Methods:

Patients undergoing elective 1 to 2 level lumbar fusion were identified using the Health Care Utilization Project (HCUP) state inpatient databases from Florida and California. Patients were tracked for 5 years for any subsequent lumbar fusion. Cox proportional hazard analyses for reoperation were assessed using the following covariates: fusion approach type, age, race, Charlson comormidity index, gender, and length of stay. Distribution of etiologies for reoperation was then assessed.

Results:

71, 456 patients receiving elective 1 to 2 level lumbar fusion were included. A 5-year reoperation rate of 13.53% and mortality rate of 2.22% was seen. Combined anterior-posterior approaches (HR = 0.904, p < 0.05) and TLIF (HR = 0.867, p < 0.001) were associated with reduced risk of reoperation compared to stand-alone anterior approaches and non-TLIF posterior approaches. Age, gender, and number of comorbidities were not associated with risk of reoperation. From 1 to 5 years, degenerative disease rose from 43.50% to 50.31% of reoperations; mechanical failure decreased from 37.65% to 29.77%.

Conclusions:

TLIF and combined anterior-posterior approaches for 1 to 2 level lumbar fusion are associated with the lowest rate of reoperation. Number of comorbidities and age are not predictive of reoperation. Primary etiologies leading to reoperation were degenerative disease and mechanical failure. Mortality rate is not increased from baseline following 1 to 2 level lumbar fusion.
Return to Sport After Large Single-Surface, Multisurface, or Bipolar Osteochondral Allograft Transplantation in the Knee Using Shell Grafts
Authors: Cook James L. , Rucinski Kylee , Crecelius Cory R. , Ma Richard , Stannard James P.
Published: January 2021

Background:

Return to sport (RTS) after osteochondral allograft (OCA) transplantation for large unipolar femoral condyle defects has been consistent, but many athletes are affected by more severe lesions.

Purpose:

To examine outcomes for athletes who have undergone large single-surface, multisurface, or bipolar shell OCA transplantation in the knee.

Study Design:

Case series; Level of evidence, 4.

Methods:

Data from a prospective OCA transplantation registry were assessed for athletes who underwent knee transplantation for the first time (primary transplant) between June 2015 and March 2018 for injury or overuse-related articular defects. Inclusion criteria were preinjury Tegner level ≥5 and documented type and level of sport (or elite unit active military duty); in addition, patients were required to have a minimum of 1-year follow-up outcomes, including RTS data. Patient characteristics, surgery type, Tegner level, RTS, patient-reported outcome measures (PROMs), compliance with rehabilitation, revisions, and failures were assessed and compared for statistically significant differences.

Results:

There were 37 included athletes (mean age, 34 years; range, 15-69 years; mean body mass index, 26.2 kg/m2; range, 18-35 kg/m2) who underwent large single-surface (n = 17), multisurface (n = 4), or bipolar (n = 16) OCA transplantation. The highest preinjury median Tegner level was 9 (mean, 7.9 ± 1.7; range, 5-10). At the final follow-up, 25 patients (68%) had returned to sport; 17 (68%) returned to the same or higher level of sport compared with the highest preinjury level. The median time to RTS was 16 months (range, 7-26 months). Elite unit military, competitive collegiate, and competitive high school athletes returned at a significantly higher proportion ( P < .046) than did recreational athletes. For all patients, the Tegner level at the final follow-up (median, 6; mean, 6.1 ± 2.7; range, 1-10) was significantly lower than that at the highest preinjury level ( P = .007). PROMs were significantly improved at the final follow-up compared with preoperative levels and reached or exceeded clinically meaningful differences. OCA revisions were performed in 2 patients (5%), and failures requiring total knee arthroplasty occurred in 2 patients (5%), all of whom were recreational athletes. Noncompliance was documented in 4 athletes (11%) and was 15.5 times more likely ( P = .049) to be associated with failure or a need for revision than for compliant patients.

Conclusion:

Large single-surface, multisurface, or bipolar shell OCA knee transplantations in athletes resulted in two-thirds of these patients returning to sport at 16 to 24 months after transplantation. Combined, the revision and failure rates were 10%; thus, 90% of patients were considered to have successful 2- to 4-year outcomes with significant improvements in pain and function, even when patients did not RTS.
Third-Generation Autologous Chondrocyte Implantation at the Knee Joint Using the Igor Scaffold: A Case Series With 2-Year Follow-up
Authors: Zak Lukas , Kleiner Anne , Albrecht Christian , Tichy Brigitte , Aldrian Silke
Published: January 2021

Background:

For large, locally restricted cartilage defects in young patients, third-generation matrix-supported autologous chondrocyte implantation (ACI) with a variety of scaffolds has shown good mid- to long-term results.

Purpose/Hypothesis:

This study aimed to monitor the clinical and radiological outcomes of patients who received ACI at the knee joint using the Igor scaffold (IGOR–Institute for Tissue and Organ Reconstruction) at 2-year follow-up. Our hypothesis was that there would be improvements in postoperative subjective scores and cartilage repair tissue quality.

Study Design:

Case series; Level of evidence, 4.

Methods:

A total of 21 patients (12 male and 9 female) were available for 2-year follow-up after third-generation ACI using the Igor scaffold. All were clinically assessed using the Knee injury and Osteoarthritis Outcome Score (KOOS), Tegner Activity Scale, Brittberg score, International Knee Documentation Committee (IKDC) Subjective Knee Form, Noyes Sports Activity Rating Scale, and visual analog scale for pain. For morphological evaluation, the magnetic resonance observation of cartilage repair tissue (MOCART) and MOCART 2.0 scores were calculated using 3-T magnetic resonance imaging performed at 3, 6, 12, and 24 months postoperatively. Results were compared between baseline and 24 months postoperatively.

Results:

After 2 years, the clinical and radiological scores showed good to excellent results in the majority of patients. On the IKDC, 10 patients were graded as excellent, 4 as good, 5 as fair, and 2 as severe; on the KOOS, 7 patients were graded as excellent, 8 as good, 4 as fair, and 2 as severe. From baseline to latest follow-up, visual analog scale pain scores decreased from 5.6 ± 3.2 (mean ± SD) to 1.5 ± 2; KOOS results increased from 51 ± 20.7 to 75.2 ± 15.4; and the Tegner score improved from 2.2 ± 1.8 to 4.3 ± 1.3. The MOCART and MOCART 2.0 scores were comparable at 2-year follow-up, with mean values of 74 ± 10 and 78 ± 13, respectively. Satisfactory filling and integration were found in 90.5%. Overall, 16 of 21 patients (76.1%) were satisfied with the surgery and would undergo the procedure again.

Conclusion:

Third-generation ACI using the Igor scaffold showed improvements in clinical and radiological results that were comparable with other scaffolds for patients with large traumatic or degenerative cartilage defects. Patients reported a decrease in pain and an increase in activity, with the majority reporting good results.
Return to Play Rates in NFL Wide Receivers and Running Backs After ACL Reconstruction: An Updated Analysis
Authors: Manoharan Aditya , Barton Dane , Khwaja Ansab , Latt L. Daniel
Published: January 2021

Background:

Anterior cruciate ligament (ACL) ruptures are potentially career-threatening injuries to National Football League (NFL) skill position players. A 2006 study showed a return-to-play (RTP) rate of 79% for NFL running backs (RBs) and wide receivers (WRs). Since then, a number of factors affecting RTP, including style of play as well as rules regarding hits to the head, have changed how defensive players tackle offensive ball carriers.

Purpose/Hypothesis:

To determine whether the RTP rate for RBs and WRs in the NFL has changed since data were collected in the 2000s. Additionally, we evaluated player performance before and after ACL reconstruction (ACLR). We hypothesized that there will be a lower RTP rate than previously reported as well as a decrease in performance statistics after ACLR.

Study Design:

Descriptive epidemiology study.

Methods:

Publicly available NFL injury reports between the 2009-2010 and 2015-2016 seasons were utilized for RBs and WRs who underwent ACLR. Successful RTP was indicated by playing in at least 1 NFL game after reconstruction. Position-specific performance statistics from before and after reconstruction were gathered for these players, and the RTP players were compared against the players who did not RTP (dnRTP group). Pre- and postinjury performance measures were also compared against a matched control group of NFL RBs and WRs who had not sustained an ACL injury.

Results:

Overall, 61.8% of players (64.5% of RBs, 60% of WRs) returned to play at a mean of 13.6 months. Prior to injury, the RTP group had played in significantly more career games and had significantly more rushes and receptions per game than the dnRTP group; however, there was no significant difference in performance after ACLR. The WR RTP group had significantly decreased performance in all measured categories when compared with the control group.

Conclusion:

Our study found a lower RTP rate in RBs and WRs than previous studies conducted in the early 2000s. WRs who achieved RTP had decreased performance when compared with noninjured controls.
Tibial Tubercle Osteotomy With Distalization Is a Safe and Effective Procedure for Patients With Patella Alta and Patellar Instability
Authors: Leite Chilan B.G. , Santos Társis P. , Giglio Pedro N. , Pécora José R. , Camanho Gilberto L. , Gobbi Riccardo G.
Published: January 2021

Background:

Tibial tubercle osteotomy with concomitant distalization for the treatment of patellar instability remains controversial, as it may cause anterior knee pain and chondral degeneration.

Purpose:

To evaluate radiographic, clinical, and functional outcomes in patients who had patellar instability with patella alta and underwent tibial tubercle osteotomy with distalization (TTO-d) as well as medial patellofemoral ligament reconstruction.

Study Design:

Case series; Level of evidence, 4.

Methods:

Included in this study were 25 patients (31 cases) (mean age at surgery, 28.7 years; range, 14-33 years) with patellar instability and patella alta who underwent TTO-d with minimum 1-year follow-up. The Caton-Deschamps index (CDI), tibial tubercle–trochlear groove (TT-TG) distance, and amount of distalization were assessed. Clinical and functional variables included J-sign, anterior knee pain, apprehension test, Tegner activity level, and Kujala score.

Results:

The mean follow-up period was 2.62 years. The mean TT-TG was 16.15 mm (range, 7-24 mm); the mean CDI changed from 1.37 (1.25-1.7) preoperatively to 1.02 (0.9-1.12) postoperatively ( P = .001); and the mean amount of tibial tubercle distalization was 8.80 mm (range, 4-16 mm). Lateral release (22 cases; 71.0%), medialization of tibial tubercle (17 cases; 54.8%), and autologous chondrocyte implantation (4 cases; 12.9%) were other associated procedures. The J-sign improved in 30 cases (96.8%; P = .001), and there was a complete resolution of anterior knee pain in 22 cases (71.0%; P = .001). An exploratory analysis showed that patellar cartilage defect severity was correlated with persistent pain ( P = .005). The apprehension test became negative in all cases ( P = .001). The median Kujala score increased from 52 to 77 ( P = .001), and the median Tegner activity level improved from 3 to 4 ( P = .001). No cases of osteotomy nonunion were reported. One case (3.2%) of patellar instability recurrence and 3 cases (6.5%) with painful hardware were observed.

Conclusion:

TTO-d resulted in good radiographic, clinical, and functional outcomes providing proper patellar stability to patients with patella alta. TTO-d appears to be a safe and efficient procedure with low complication rates, providing an additional tool for the personalized treatment of patellar instability.
Early Outcomes of Adolescent ACL Reconstruction With Hybrid Hamstring Tendon Autograft-Allograft Versus Hamstring Tendon Autograft Alone
Authors: Heyworth Benton E. , Zheng Evan T. , Vavken Patrick , Liotta Elizabeth S. , Kramer Dennis E. , Yen Yi-Meng , Micheli Lyle J. , Kocher Mininder S.
Published: January 2021

Background:

Small-diameter semitendinosus-gracilis tendon autografts may be encountered intraoperatively during anterior cruciate ligament reconstruction (ACLR); these have been shown to be at increased risk of graft rupture. One option that surgeons have pursued to reduce the theoretical failure rate of these smaller-diameter grafts is augmenting them with allograft material, thereby forming a larger-diameter hybrid autograft-allograft construct.

Purpose/Hypothesis:

The purpose of this study was to compare outcomes in adolescent athletes of primary ACLR using a hybrid autologous hamstring tendon and soft tissue allograft construct versus ACLR using small-diameter hamstring tendon autograft. The hypothesis was that the hybrid hamstring autograft-allograft construct would provide superior short-term results.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

We performed a retrospective analysis of 47 patients aged between 12 and 20 years who underwent hybrid graft ACLR (mean diameter, 9.1 mm) at a single institution. Electronic medical records including clinic notes, radiographic images, operative notes, and pathology reports were reviewed for study analysis. A control group of 64 patients who underwent small-diameter hamstring reconstruction (mean diameter, 7.1 mm) without allograft supplementation was compiled. Corresponding clinical, radiographic, and surgical characteristics were collected for the control group to allow for comparative analysis.

Results:

Mean follow-up was 2.7 years for the hybrid cohort and 2.3 years for the control group. Despite a significantly larger mean graft diameter in the hybrid group as compared with the control group ( P < .001), no significant difference in retear rate was seen between cohorts (hybrid, 9%; control, 13%; P = .554). Patients with hybrid anterior cruciate ligament constructs also underwent a comparable number of reoperations overall ( P = .838). Functionally, all patients with adequate follow-up returned to sports, with no significant difference in time to return to sports between the groups ( P = .213). Radiographically, hybrid graft constructs did not undergo a significantly larger degree of tunnel lysis ( P = .126).

Conclusion:

A cohort of adolescents with hybrid anterior cruciate ligament grafts was shown to have retear rates and overall clinical results comparable with those of a control group that received small-diameter hamstring tendon autografts alone.
Context of Reception and School Violence: Exploring the Nexus of Immigration, Race/Ethnicity, Place, and School Crime
Authors: Peguero Anthony A. , Irizarry Yasmiyn , Iwama Janice A. , Dunning-Lozano Jessica L. , Sung Hong Jun , King Sanna
Published: January 2021

Of course, ensuring safe environments in the U.S. educational system is paramount. It is also evident, however, inequalities associated with immigration, race/ethnicity, and situational context can impede school safety pursuits. Although prior research has revealed a pattern between “downward” assimilation and increased experiences with student-level violence and disorder for the children of racial/ethnic immigrants (i.e., first- and second-generation), investigations about school-level rates of violence and disorder associated with the context of reception remain uncertain. Our study seeks to contribute to the research about immigration, racial/ethnic inequality, education, and violence by examining the associations between context, school violence, and crime, and the schooling of children of immigrants by drawing on a context of reception conceptual framework to address three research questions. First, is there an association between an increasing proportion of children of immigrants and school crimes (i.e., violence, property damage, and substance use)? Second, are there differences linked to the context of reception (i.e., urban, suburban, town, and rural) in the association between the increasing proportion of children of immigrants and school crime? Third, are there racial/ethnic differences in the association between the increasing proportion of children of immigrants and school crimes in distinct contexts? Findings indicate that the children of racial/ethnic minority immigrants have significantly distinct associations with rates of school violence and crime across all contexts; however, there are important and distinctive nuances that are presented and examined.
Assessment of Clinical Leadership Training Needs in Senior Pediatric Residents
Authors: Mai Daniel H , Newton Heather , Farrell Peter R , Mullan Paul , Kapoor Rupa
Published: January 2021

Introduction:

Although clinical leadership in physicians is associated with improved healthcare, leadership training is rarely integrated into residency training. Our objective was to perform a comprehensive needs assessment of our pediatric residents’ existing leadership experiences and knowledge and to identify training gaps within our program.

Methods:

First, we held focus groups with senior pediatric residents to understand their clinical leadership experiences and identify training needs. Notes were transcribed and independently coded by 2 researchers, with thematic saturation achieved. Next, we focused each session on 1 leadership content area identified from the aforementioned themes to better understand the specific training needs for each topic.

Results:

Four major themes were identified: (1) Effective and timely communication with supervisors, learners, ancillary staff, and patients is indispensable in promoting safe patient care, avoiding conflict, and preventing misunderstanding. (2) Training in teaching methods is desired, especially gaining the skills needed to teach various levels of learners, in different settings and under time constraints. (3) Time management, availability of resources, and team logistics were often learned through trial-and-error. (4) Self-care, self-acceptance, emotional regulation, and peer debriefing are relied upon to manage negative emotions; rarely are resilience and wellness strategies employed in “real-time.”

Conclusion:

Senior residents currently face gaps in clinical leadership training and may benefit from additional instruction in content areas related to these 4 themes. Our next steps are to utilize the identified themes to develop a longitudinal and skills-based clinical leadership curriculum to address the gap in graduate medical education.
A phase 1 study of a novel fully human BCMA-targeting CAR (CT103A) in patients with relapsed/refractory multiple myeloma
Authors: Wang Di , Wang Jue , Hu Guang , Wang Wen , Xiao Yi , Cai Haodong , Jiang Lijun , Meng Li , Yang Yongkun , Zhou Xiaoxi , Hong Zhenya , Yao Zheng , Xiao Min , Chen Liting , Mao Xia , Zhu Li , Wang Jin , Qiu Lugui , Li Chunrui , Zhou Jianfeng
Published: January 2021

B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies have shown efficacy in relapsed/refractory multiple myeloma (RRMM). Because the non-human originated antigen-targeting domain may limit clinical efficacy, we developed a fully human BCMA-specific CAR, CT103A, and report its safety and efficacy in a phase 1 trial. Eighteen consecutive patients with RRMM, including 4 with prior murine BCMA CAR exposures, were enrolled. CT103A was administered at 1, 3, and 6 × 106 CAR-positive T cells/kg in the dose-escalation phase, and 1 × 106 CAR-positive T cells/kg in the expansion cohort. The overall response rate was 100%, with 72.2% of the patients achieving complete response or stringent complete response. For the 4 murine BCMA CAR–exposed patients, 3 achieved stringent complete response, and 1 achieved a very good partial response. At 1 year, the progression-free survival rate was 58.3% for all cohorts and 79.1% for the patients without extramedullary myeloma. Hematologic toxicities were the most common adverse events; 70.6% of the patients experienced grade 1 or 2 cytokine release syndromes. No immune effector cell–associated neurotoxicity syndrome was observed. To the cutoff date, CAR transgenes were detectable in 77.8% of the patients. The median CAR transgene persistence was 307.5 days. Only 1 patient was positive for the anti-drug antibody. Altogether, CT103A is safe and highly active in patients with RRMM and can be developed as a promising therapy for RRMM. Patients who relapsed from prior murine BCMA CAR T-cell therapy may still benefit from CT103A. This trial was registered at http://www.chictr.org.cn as #ChiCTR1800018137.
Photoelectronic Properties of End-bonded InAsSb Nanowire Array Detector under Weak Light
Authors: Yao Xiaomei , Zhang Xutao , Kang Tingting , Song Zhiyong , Sun Qiang , Wei Dongdong , Zou Jin , Chen Pingping
Published: January 2021

A simple fabrication of end-bonded contacts InAsSb NW (nanowire) array detector to weak light is demonstrated in this study. The detector is fabricated using InAsSb NW array grown by molecular beam epitaxy on GaAs substrate. The metal-induced gap states are induced by the end-bonded contact which suppresses the dark current at various temperatures. The existence of the interface dipole due to the interfacial gap states enhances the light excitation around the local field and thus upgrades the photoresponsivity and photodetectivity to the weak light. The light intensity of the infrared light source in this report is 14 nW/cm2 which is about 3 to 4 orders of magnitude less than the laser source. The responsivity of the detector has reached 28.57 A/W at room temperature with the light (945 nm) radiation, while the detectivity is 4.81 × 1011 cm·Hz1/2 W−1. Anomalous temperature-dependent performance emerges at the variable temperature experiments, and we discussed the detailed mechanism behind the nonlinear relationship between the photoresponse of the device and temperatures. Besides, the optoelectronic characteristics of the detector clarified that the light-trapping effect and photogating effect of the NWs can enhance the photoresponse to the weak light across ultraviolet to near-infrared. These results highlight the feasibility of the InAsSb NW array detector to the infrared weak light without a cooling system.
Functional outcome after neonatal pyeloplasty in antenatally diagnosed uretero-pelvic junction obstruction
Authors: Bendre Pradnya Suhas , Karkera Parag Janardhan , Nanjappa Monita
Published: January 2021

Background

With routine antenatal ultrasonography, fetal hydronephrosis is commonly diagnosed. This leads to early detection of postnatal uretero-pelvic junction obstruction which may require surgical intervention. But, there is no clear consensus in the benefits of operating these patients in the neonatal age.

Methods

Aim—To study the functional outcome after pyeloplasty in neonates with antenatally diagnosed unilateral uretero-pelvic junction obstruction (UPJO). Records of all neonates (N = 48) who presented between 2016 and 2018 with prenatal diagnosis of unilateral UPJO and underwent a Anderson-Hyne’s Pyeloplasty were retrospectively analyzed. Indications for surgery were SFU grade 3 or 4, a split renal function (SRF) < 40% on a diuretic renal scan and antero-posterior renal pelvic diameter (APD) > 2.5 cm with parenchymal thinning. Parenchymal thickness (PT) and APD measured by ultrasonography, and SRF measured by 99 m Tc-EC renal scan were compared before and after surgery.

Results

Our study comprised of 48 patients with 79.2% males (n = 38). UPJO affected the left side more (n = 30, 62.5%). The mean age at pyeloplasty was 28 days (range 26–30). The outcome was considered successful in 46 (95.84%) patients. The APD decreased from a mean of 3.5 cm APD preoperatively to 1.38 cm 1 year later which was statistically significant (p < 0.001). The PT increased from 3.95 to 7.1 mm 1 year postoperatively which was significant (p < 0.001). The drainage pattern and SRF improved in 46 (95.84%) patients. The SRF improved from a mean of 35.48–44.7% 1 year postoperatively which was significant (p < 0.001).

Conclusion

Pyeloplasty done in the neonatal age for prenatally diagnosed UPJO, having SFU grade 3–4 UPJO, leads to significant improvement of SRF and PT with minimal complications. Neonatal Pyeloplasty for significant UPJO is a safe procedure which provides the kidney maximum opportunity to improve function.
Predictors of urogenital distress and impaired quality of life in adult Egyptians with lower urinary tract symptoms
Authors: Wasfy Isaac Samir , Soltan Enayat Mohamed , Abdelwahab Hassan A. , Salama Hend Mikhail
Published: January 2021

Background

This study aims to assess the severity of lower urinary tract symptoms, and to assess predictors of impaired quality of life among Egyptian adults complain of lower urinary tract symptoms.

Methods

An observational cross-sectional research was done using an online anonymous poll survey. The survey was implemented through sharing on different social media applications. The survey was posted from June 1, 2020, to June 10, 2020. The overall communities of the Egyptian adults who satisfied the incorporation rules and consented to take an interest in the research were incorporated using convenience and snowball collecting methods (188 adults). A semi-structured questionnaire on socio-demographic characteristics and Arabic Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire (IIQ-7) short forms were used.

Results

Approximately 220 Egyptian adults shared in the research but only 188 fulfilled inclusion and exclusion criteria. Approximately 92% of them had at least one symptom of lower urinary tract manifestations. Irritative symptoms presented in 65 (85.5%) of males and 102 (91.1%) of females. Stress symptoms presented in 44 (57.9%) of males and 63 (56.2%) of females with higher statistically significant mean of stress symptoms. Obstruction/discomfort symptoms presented in 51 (67.1%) of males, and 77 (68.8%) of females. Seeking help and duration of the urological problem were statistically significant independent positive predictors of UDI-6-total. The Irritative score, obstruction/discomfort score, and duration of the urological problem were statistically significant independent positive predictors of IIQ-7-total.

Conclusions

Urological problems are common and have an impact on the quality of life in various domains of physical activity, social relationships, travel, and emotional health.
BSR-Seq analysis provides insights into the cold stress response of Actinidia arguta F1 populations
Authors: Lin Miaomiao , Sun Shihang , Fang Jinbao , Qi Xiujuan , Sun Leiming , Zhong Yunpeng , Sun Yanxiang , Hong Gu , Wang Ran , Li Yukuo
Published: January 2021

Background

Freezing injury, which is an important abiotic stress in horticultural crops, influences the growth and development and the production area of kiwifruit (ActinidiaLind1). AmongActinidiaspecies,Actinidia argutahas excellent cold resistance, but knowledge relevant to molecular mechanisms is still limited. Understanding the mechanism underlying cold resistance in kiwifruit is important for breeding cold resistance.

Results

In our study, a population resulting from the cross ofA. arguta‘Ruby-3’ × ‘Kuilv’ male was generated for kiwifruit hardiness study, and 20 cold-tolerant and 20 cold-sensitive populations were selected from 492 populations according to their LT50. Then, we performed bulked segregant RNA-seq combined with single-molecule real-time sequencing to identify differentially expressed genes that provide cold hardiness. We found that the content of soluble sucrose and the activity of β-amylase were higher in the cold-tolerant population than in the cold-sensitive population. Upon − 30 °C low-temperature treatment, 126 differentially expressed genes were identify; the expression of 59 genes was up-regulated and that of 67 genes was down-regulated between the tolerant and sensitive pools, respectively. KEGG pathway analysis showed that the DEGs were primarily related to starch and sucrose metabolism, amino sugar and nucleotide sugar metabolism. Ten major key enzyme-encoding genes and two regulatory genes were up-regulated in the tolerant pool, and regulatory genes of theCBFpathway were found to be differentially expressed. In particular, a14–3-3gene was down-regulated and anEBFgene was up-regulated.To validate the BSR-Seq results, 24 DEGs were assessed via qRT-PCR, and the results were consistent with those obtained by BSR-Seq.

Conclusion

Our research provides valuable insights into the mechanism related to cold resistance inActinidiaand identified potential genes that are important for cold resistance in kiwifruit.
Transcriptomic and chemical analyses to identify candidate genes involved in color variation of sainfoin flowers
Authors: Qiao Yu , Cheng Qiming , Zhang Yutong , Yan Wei , Yi Fengyan , Shi Fengling
Published: January 2021

Background

Sainfoin (Onobrychis viciifolia Scop) is not only a high-quality legume forage, but also a nectar-producing plant. Therefore, the flower color of sainfoin is an important agronomic trait, but the factors affecting its flower phenotype are still unclear. To gain insights into the regulatory networks associated with metabolic pathways of coloration compounds (flavonoids or anthocyanins) and identify the key genes, we conducted a comprehensive analysis of the phenotype, metabolome and transcriptome of WF and AF of sainfoin.

Results

Delphinidin, petunidin and malvidin derivatives were the main anthocyanin compounds in the AF of sainfoin. These substances were not detected in the WF of sainfoin. The transcriptomes of WF and AF in sainfoin at the S1 and S3 stages were obtained using the Illumina HiSeq4000 platform. Overall, 10,166 (4273 upregulated and 5893 downregulated) and 15,334 (8174 upregulated and 7160 downregulated) DEGs were identified in flowers at S1 and S3 stages, respectively (WF-VS-AF). KEGG pathway annotations showed that 6396 unigenes were annotated to 120 pathways and contained 866 DEGs at S1 stages, and 6396 unigenes were annotated to 131 pathways and included 1546 DEGs at the S3 stage. Nine DEGs belonging to the “flavonoid biosynthesis”and “phenylpropanoid biosynthesis” pathways involved in flower color formation were identified and verified by RT-qPCR analyses. Among these DEGs, 4CL3, FLS, ANS, CHS, DFR and CHI2 exhibited downregulated expression, and F3H exhibited upregulated expression in the WF compared to the AF, resulting in a decrease in anthocyanin synthesis and the formation of WF in sainfoin.

Conclusions

This study is the first to use transcriptome technology to study the mechanism of white flower formation in sainfoin. Our transcriptome data will be a great enrichment of the genetic information for sainfoin. In addition, the data presented herein will provide valuable molecular information for genetic breeding and provide insight into the future study of flower color polymorphisms in sainfoin.
An improved and efficient method of Agrobacterium syringe infiltration for transient transformation and its application in the elucidation of gene function in poplar
Authors: Zheng Lin , Yang Jixiu , Chen Yajuan , Ding Liping , Wei Jianhua , Wang Hongzhi
Published: January 2021

Background

Forest trees have important economic and ecological value. As a model tree, poplar has played a significant role in elucidating the molecular mechanisms underlying tree biology. However, a lack of mutant libraries and time-consuming stable genetic transformation processes severely limit progress into the functional characterization of poplar genes. A convenient and fast transient transformation method is therefore needed to enhance progress on functional genomics in poplar.

Methods

A total of 11 poplar clones were screened for amenability to syringe infiltration. Syringe infiltration was performed on the lower side of the leaves of young soil-grown plants. Transient expression was evaluated by visualizing the reporters β-glucuronidase (GUS) and green fluorescent protein (GFP). The experimental parameters of the syringe agroinfiltration were optimized based on the expression levels of the reporter luciferase (LUC). Stably transformed plants were regenerated from transiently transformed leaf explants through callus-induced organogenesis. The functions of Populus genes in secondary cell wall-thickening were characterized by visualizing lignin deposition therein after staining with basic fuchsin.

Results

We greatly improved the transient transformation efficiency of syringe Agrobacterium infiltration in poplar through screening for a suitable poplar clone from a variety of clones and optimizing the syringe infiltration procedure. The selected poplar clone, Populus davidiana × P. bolleana, is amenable to Agrobacterium syringe infiltration, as indicated by the easy diffusion of the bacterial suspension inside the leaf tissues. Using this technique, we localized a variety of poplar proteins in specific intracellular organelles and illustrated the protein–protein and protein–DNA interactions. The transiently transformed leaves could be used to generate stably transformed plants with high efficiency through callus induction and differentiation processes. Furthermore, transdifferentiation of the protoxylem-like vessel element and ectopic secondary wall thickening were induced in the agroinfiltrated leaves via the transient overexpression of genes associated with secondary wall formation.

Conclusions

The application of P. davidiana × P. bolleana in Agrobacterium syringe infiltration provides a foundation for the rapid and high-throughput functional characterization of Populus genes in intact poplar plants, including those involved in wood formation, and provides an effective alternative to Populus stable genetic transformation.
Heterologous expression of Arabidopsis thaliana rty gene in strawberry (Fragaria × ananassa Duch.) improves drought tolerance
Authors: Li Maofu , Yang Yuan , Raza Ali , Yin Shanshan , Wang Hua , Zhang Yuntao , Dong Jing , Wang Guixia , Zhong Chuanfei , Zhang Hong , Liu Jiashen , Jin Wanmei
Published: January 2021

Background

Strawberry (Fragaria × ananassa Duch.) is an important fruit crop worldwide. It was particularly sensitive to drought stress because of their fibrous and shallow root systems. Mutant rty of Arabidopsis thaliana ROOTY (RTY) results in increased endogenous auxin levels, more roots, and shoot growth. It is still unclear whether the rty gene improves stress tolerance in strawberry.

Results

rty gene was isolated from Arabidopsis thaliana and placed under the control of the cauliflower mosaic virus (CaMV) 35S promoter in the pBI121-rty binary vector carrying the selectable marker of neomycin phosphotransferase II (NPT II). Seven transgenic lines were confirmed by PCR and western blot analysis. Accumulations of IAA and ABA were significantly increased in the transgenic plants. The endogenous IAA contents were 46.5 ng g− 1 and 66.0 ng g− 1in control and transgenic plants respectively. The endogenous ABA contents in the control plant were 236.3 ng g− 1 and in transgenic plants were 543.8 ng g− 1. The production of adventitious roots and trichomes were enhanced in the transgenic plants. Furthermore, transcript levels of the genes including IAA and ABA biosynthetic, and stress-responsive genes, were higher in the transgenic plants than in the control plants under drought conditions. Water use efficiency and a reduced water loss rate were enhanced in the transgenic strawberry plants. Additionally, peroxidase and catalase activities were significantly higher in the transgenic plants than in the control plants. The experiment results revealed a novel function for rty related to ABA and drought responses.

Conclusions

The rty gene improved hormone-mediated drought tolerance in transgenic strawberry. The heterologous expression of rty in strawberry improved drought tolerance by promoting auxin and ABA accumulation. These phytohormones together brought about various physiological changes that improved drought tolerance via increased root production, trichome density, and stomatal closure. Our results suggested that a transgenic approach can be used to overcome the inherent trade-off between plant growth and drought tolerance by enhancing water use efficiency and reducing water loss rate under water shortage conditions.
Diagnostic accuracy of a liquid chromatography-tandem mass spectrometry assay in small hair samples for rifampin-resistant tuberculosis drug concentrations in a routine care setting
Authors: Metcalfe John , Bacchetti Peter , Esmail Ali , Reckers Andrew , Aguilar David , Wen Anita , Huo Shu , Muyindike Winnie R. , Hahn Judith A. , Dheda Keertan , Gandhi Monica , Gerona Roy
Published: January 2021

Background

Treatment monitoring of drug-resistant tuberculosis (DR-TB) in resource-limited settings is challenging. We developed a multi-analyte assay for eleven anti-TB drugs in small hair samples as an objective metric of drug exposure.

Methods

Small hair samples were collected from participants at various timepoints during directly observed RR-TB treatment at an inpatient tertiary referral facility in South Africa (DR-TB cohort). We assessed qualitative determination (i.e., detection above limit of detection) of bedaquiline, linezolid, clofazimine, pretomanid, levofloxacin, moxifloxacin, pyrazinamide, isoniazid, ethambutol, ethionamide, and prothionamide in an LC-MS/MS index panel assay against a reference standard of inpatient treatment records. Because treatment regimens prior to hospitalization were not available, we also analyzed specificity (for all drugs except isoniazid) using an external cohort of HIV-positive patients treated for latent TB infection with daily isoniazid (HIV/LTBI cohort) in Uganda.

Results

Among the 57 DR-TB patients (58% with pre-XDR/XDR-TB; 70% HIV-positive) contributing analyzable hair samples, the sensitivity of the investigational assay was 94% or higher for all drugs except ethionamide (58.5, 95% confidence interval [CI], 40.7–99.9). Assay specificity was low across all tested analytes within the DR-TB cohort; conversely, assay specificity was 100% for all drugs in the HIV/LTBI cohort.

Conclusions

Hair drug concentrations reflect long-term exposure, and multiple successive regimens commonly employed in DR-TB treatment may result in apparent false-positive qualitative and falsely elevated quantitative hair drug levels when prior treatment histories within the hair growth window are not known.