bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retreatment of Patients With Metastatic Cutaneous Melanoma Who Relapse After Elective Checkpoint Inhibitor Discontinuation After a Complete Remission
Authors: Sadrolashrafi Kaviyon , Samlowski Wolfram 
Published: February 2023

Abstract

Introduction
Checkpoint blockade has improved the response rate and survival in metastatic melanoma. Elective treatment discontinuation appears to be reasonable in most patients who have achieved a confirmed complete remission. It seems crucial to understand whether restarting immune checkpoint inhibitor therapy can induce additional responses or remissions in rare patients who relapse.

Methods
A retrospective analysis identified only 10 patients who relapsed after elective treatment discontinuation after a radiologically confirmed remission. These patients were retreated with single-agent PD-1 or combined CTLA-4 plus PD-1-directed monoclonal antibodies.

Results
We found an initial complete response rate of 20% (2 patients) following retreatment. With a median follow-up of 26 months, the addition of individualized salvage therapies converted an additional 4 patients to a 2nd remission. All 6 of these patients have again discontinued therapy. Three patients have died of metastatic melanoma, while another is receiving salvage therapy. Six of our 10 patients experienced grades 2-3 retreatment-related toxicity. There were no hospitalizations or fatalities.

Discussion
Retreatment of relapsing patients resulted in 20% complete responses with checkpoint inhibitors. The planned addition of other treatment modalities converted another 4 patients (40%) to a durable 2nd remission. This sequential approach merits further exploration in prospective clinical trials.
Loss of CpFTSY Reduces Photosynthetic Performance and Affects Insertion of PsaC of PSI in Diatoms
Authors: Nymark Marianne , Finazzi Giovanni , Volpe Charlotte , Serif Manuel , Fonseca Davi de Miranda , Sharma Animesh , Sanchez Nicolas , Sharma Amit Kumar , Ashcroft Felicity , Kissen Ralph , Winge Per , Bones Atle Magnar 
Published: February 2023

Abstract
The chloroplast signal recognition particle (CpSRP) receptor (CpFTSY) is a component of the CpSRP pathway that post-translationally targets light-harvesting complex proteins (LHCPs) to the thylakoid membranes in plants and green algae containing chloroplasts derived from primary endosymbiosis. In plants, CpFTSY also plays a major role in the co-translational incorporation of chloroplast-encoded subunits of photosynthetic complexes into the thylakoids. This role has not been demonstrated in green algae. So far, its function in organisms with chloroplasts derived from secondary endosymbiotic events has not been elucidated. Here, we report the generation and characterization of mutants lacking CpFTSY in the diatom Phaeodactylum tricornutum. We found that this protein is not involved in inserting LHCPs into thylakoid membranes, indicating that the post-translational part of the CpSRP pathway is not active in this group of microalgae. The lack of CpFTSY caused an increased level of photoprotection, low electron transport rates, inefficient repair of photosystem II (PSII), reduced growth, a strong decline in the PSI subunit PsaC and upregulation of proteins that might compensate for a non-functional co-translational CpSRP pathway during light stress conditions. The phenotype was highly similar to the one described for diatoms lacking another component of the co-translational CpSRP pathway, the CpSRP54 protein. However, in contrast to cpsrp54 mutants, only one thylakoid membrane protein, PetD of the Cytb6f complex, was downregulated in cpftsy. Our results point to a minor role for CpFTSY in the co-translational CpSRP pathway, suggesting that other mechanisms may partially compensate for the effect of a disrupted CpSRP pathway.
MEDIATOR SUBUNIT17 is required for transcriptional optimization of root system architecture in Arabidopsis
Authors: Agrawal Rekha , Singh Amrita , Giri Jitender , Magyar Zoltan , Thakur Jitendra Kumar 
Published: February 2023

Abstract
Sucrose and auxin are well-known determinants of root system architecture (RSA). However, the factors that connect the signaling pathways evoked by these two critical factors during root development are poorly understood. In this study, we report the role of MEDIATOR SUBUNIT17 (MED17) in RSA and its involvement in the transcriptional integration of sugar and auxin signaling pathways in Arabidopsis (Arabidopsis thaliana). Sucrose regulates root meristem activation through the TARGET OF RAPAMYCIN-E2 PROMOTER BINDING FACTOR A (TOR-E2FA) pathway, and auxin regulates lateral root (LR) development through AUXIN RESPONSE FACTOR-LATERAL ORGAN BOUNDARIES DOMAIN (ARF-LBDs). Both sucrose and auxin play a vital role during primary and LR development. However, there is no clarity on how sucrose is involved in the ARF-dependent regulation of auxin-responsive genes. This study establishes MED17 as a nodal point to connect sucrose and auxin signaling. Transcription of MED17 was induced by sucrose in an E2FA/B-dependent manner. Moreover, E2FA/B interacted with MED17, which can aid in the recruitment of the Mediator complex on the target promoters. Interestingly, E2FA/B and MED17 also occupied the promoter of ARF7, but not ARF19, leading to ARF7 expression, which then activates auxin signaling and thus initiates LR development. MED17 also activated cell division in the root meristem by occupying the promoters of cell–cycle genes, thus regulating their transcription. Thus, MED17 plays an important role in relaying the transcriptional signal from sucrose to auxin-responsive and cell–cycle genes to regulate primary and lateral root development, highlighting the role of the Mediator as the transcriptional processor for optimal root system architecture in Arabidopsis.
Autophagy and multivesicular body pathways cooperate to protect sulfur assimilation and chloroplast functions
Authors: Fu Yunting , Fan Baofang , Li Xifeng , Bao Hexigeduleng , Zhu Cheng , Chen Zhixiang 
Published: February 2023

Abstract
Autophagy and multivesicular bodies (MVBs) represent 2 closely related lysosomal/vacuolar degradation pathways. In Arabidopsis (Arabidopsis thaliana), autophagy is stress-induced, with deficiency in autophagy causing strong defects in stress responses but limited effects on growth. LYST-INTERACTING PROTEIN 5 (LIP5) is a key regulator of stress-induced MVB biogenesis, and mutation of LIP5 also strongly compromises stress responses with little effect on growth in Arabidopsis. To determine the functional interactions of these 2 pathways in Arabidopsis, we generated mutations in both the LIP5 and AUTOPHAGY-RELATED PROTEIN (ATG) genes. atg5/lip5 and atg7/lip5 double mutants displayed strong synergistic phenotypes in fitness characterized by stunted growth, early senescence, reduced survival, and greatly diminished seed production under normal growth conditions. Transcriptome and metabolite analysis revealed that chloroplast sulfate assimilation was specifically downregulated at early seedling stages in the atg7/lip5 double mutant prior to the onset of visible phenotypes. Overexpression of adenosine 5′-phosphosulfate reductase 1, a key enzyme in sulfate assimilation, substantially improved the growth and fitness of the atg7/lip5 double mutant. Comparative multi-omic analysis further revealed that the atg7/lip5 double mutant was strongly compromised in other chloroplast functions including photosynthesis and primary carbon metabolism. Premature senescence and reduced survival of atg/lip5 double mutants were associated with increased accumulation of reactive oxygen species and overactivation of stress-associated programs. Blocking PHYTOALEXIN DEFICIENT 4 and salicylic acid signaling prevented early senescence and death of the atg7/lip5 double mutant. Thus, stress-responsive autophagy and MVB pathways play an important cooperative role in protecting essential chloroplast functions including sulfur assimilation under normal growth conditions to suppress salicylic-acid-dependent premature cell-death and promote plant growth and fitness.
Safety profile and technical success rate of computed tomography–guided atlanto-axial lateral articulation injections
Authors: Liou Harris , Diehn Felix E , Lehman Vance T , Murthy Naveen S , Carr Carrie M , Madhavan Ajay A , Benson John C , Oien Michael P , Kim Dong Kun 
Published: February 2023

Abstract

Objective
To describe the technique, safety profile, and outcome of computed tomography (CT)–guided atlanto-axial lateral articulation injections performed at our institution.

Methods
Consecutive cases of all CT-guided atlanto-axial injections performed from January 2017 to April 2022 at our institution were searched in the electronic medical records. Patient charts were reviewed for demographics, characterization of pain, potential altered anatomy, pain level before and immediately after the procedure, procedure technique, complications, and follow-up outcomes, if available.

Results
Forty-five injections in 40 different patients were included. The average age was 67.4 years, and 28 (70%) of the patients were female. Of the 45 injections, 43 (96%) were technically successful. The average change in pain score (0–10) from immediately before to immediately after the injection was –3.36 (SD = 2.87, range = –8 to +3). Of all injections, 14 (31%) had a postprocedural pain score of zero. In 2 cases (4%), patients reported an increase in pain score immediately after the injection. In 3 cases (7%), transient non–vertebral artery vascular uptake of contrast was documented during the procedure, which could be cleared with needle repositioning. There were no complications.

Conclusion
CT-guided atlanto-axial lateral articulation injection is a safe procedure with a high technical success rate. It allows for direct visualization of vital structures and provides an alternative option to the traditional fluoroscopic guidance, especially in cases of prior technically unsuccessful fluoroscopically guided injection or altered anatomy.
A research on the effectiveness of innovation policy for regional innovation under Chinese long-range plan
Authors: Yang Boxu , Liu Xielin , Gao Yuchen , Zhu Langmei 
Published: February 2023

Abstract
By adopting a set of panel data from thirty provinces in China from 2007 to 2017, this paper examines how regional innovation efficiency is influenced by different types of innovation policies from a specific long-range plan (‘National Medium- and Long-Term Science and Technology Development Plan (2006–20)’). We incorporate public direct research and development (R&D) grants, R&D tax credits, and intellectual property rights (IPR) protection into our research. We also explore the heterogeneous influences of these factors at different stages in regional innovation development. The results indicate that public direct R&D grants have a significantly negative influence, especially in innovation-catching-up regions. Conversely, the R&D tax credit has a considerably positive impact on innovation-catching-up regions. IPR protection plays various roles according to different innovation development stages. Specifically, IPR protection has a positive impact on innovation-leading regions, while it negatively influences regional innovation efficiency in innovation-catching-up regions.
Chromatin accessibility dynamics insight into crosstalk between regulatory landscapes in poplar responses to multiple treatments
Authors: Wang Weiwei , Chen Kai , Chen Ningning , Gao Jinwen , Zhang Wenyan , Gong Jue , Tong Shaofei , Chen Yang , Li Yiling , Feng Yanlin , Jiang Yuanzhong , Ma Tao 
Published: February 2023

Abstract
Perennial trees develop and coordinate endogenous response signaling pathways, including their crosstalk and convergence, to cope with various environmental stresses which occur simultaneously in most cases. These processes are involved in gene transcriptional regulations that depend on dynamic interactions between regulatory proteins and corresponding chromatin regions, but the mechanisms remain poorly understood in trees. In this study, we detected chromatin regulatory landscapes of poplar under abscisic acid, methyl jasmonate, salicylic acid and sodium chloride (NaCl) treatment, through integrating ATAC-seq and RNA-seq data. Our results showed that the degree of chromatin accessibility for a given gene is closely related to its expression level. However, unlike the gene expression that shows treatment-specific response patterns, changes in chromatin accessibility exhibit high similarities under these treatments. We further proposed and experimentally validated that a homologous gene copy of RESPONSIVE TO DESICCATION 26 mediates the crosstalk between jasmonic acid and NaCl signaling pathways by directly regulating the stress-responsive genes and that circadian clock-related transcription factors like REVEILLE8 play a central role in response of poplar to these treatments. Overall, our study provides a chromatin insight into the molecular mechanism of transcription regulatory networks in response to different environmental stresses and raises the key roles of the circadian clock of poplar to adapt to adverse environments.
Critères de constitution des sociétés commerciales en droit OHADA et burundais
Authors: Nzohabonayo Anaclet , Clerson Iradukunda Olivier 
Published: February 2023

Résumé
Cette réflexion a examiné les critères de légalité et d’opérationnalité qui président à la constitution des sociétés commerciales dans le droit OHADA et burundais. Le code burundais des sociétés privées et à participation publique et l’Acte uniforme portant société commerciale et groupement d’intérêt économique ont servi de supports d’analyse. L’objectif consistait à examiner les critères qui régissent la formation des sociétés commerciales dans ces espaces juridiques afin d’en préciser le contenu pour après dégager les spécificités qui les caractérisent. Au seuil de la réflexion, l’étude conclut que les deux régimes juridiques partagent en commun les grands principes de formation des sociétés commerciales. Toutefois, à l’intérieur de ces principes se trouvent certaines spécificités qui font que ces régimes se démarquent l’un de l’autre. Les différences portent notamment sur la fixation du montant du capital minimum, la société anonyme unipersonnelle, la libération des apports en numéraire et la quotité des apports en industrie et bien d’autres.
Exploring the Relationship Between Pattern-Triggered Immunity and Quantitative Resistance to Xanthomonas vasicola pv. vasculorum in Maize
Authors: Mullens Alexander , Lipka Alexander E. , Balint-Kurti Peter , Jamann Tiffany 
Published: February 2023

Bacterial leaf streak (BLS) of maize is an emerging foliar disease of maize in the Americas. It is caused by the gram-negative nonvascular bacterium Xanthomonas vasicola pv. vasculorum. There are no chemical controls available for BLS, and thus, host resistance is crucial for managing X. vasicola pv. vasculorum. The objective of this study was to examine the genetic determinants of resistance to X. vasicola pv. vasculorum in maize, as well as the relationship between other defense-related traits and BLS resistance. Specifically, we examined the correlations among BLS severity, severity for three fungal diseases, flg-22 response, hypersensitive response, and auricle color. We conducted quantitative trait locus (QTL) mapping for X. vasicola pv. vasculorum resistance using the maize recombinant inbred line population Z003 (B73 × CML228). We detected three QTLs for BLS resistance. In addition to the disease resistance QTL, we detected a single QTL for auricle color. We observed significant, yet weak, correlations among BLS severity, levels of pattern-triggered immunity response and leaf flecking. These results will be useful for understanding resistance to X. vasicola pv. vasculorum and mitigating the impact of BLS on maize yields.
Predictors of the Need for Surgery in Cervical Ossification of the Posterior Longitudinal Ligament
Authors: Masuda Soichiro , Fukasawa Toshiki , Takeuchi Masato , Fujibayashi Shunsuke , Otsuki Bungo , Murata Koichi , Shimizu Takayoshi , Matsuda Shuichi , Kawakami Koji 
Published: February 2023

Study Design:
Retrospective cohort study.

Objective:
The aim of this study was to determine predictors associated with the need
for cervical ossification of the posterior longitudinal ligament (cOPLL) surgery among
individuals with cOPLL.

Summary of Background Data:
cOPLL is a spinal disorder caused by ectopic ossification of the posterior longitudinal ligament. However, factors associated with a higher rate of surgery to treat the neurological symptoms of cOPLL are poorly understood.

Materials and Methods:
This retrospective population-based cohort study using a commercial administrative claims database from JMDC Inc. (Tokyo, Japan) enrolled patients newly diagnosed with cOPLL from April 2005 to October 2020 and followed to April 2021. A total of 1506 cOPLL patients aged 18 years or older with no history of cervical spine surgery and with a record of metabolic profiles obtained at general health checkups were included. Cox proportional hazards regression models identified patient characteristics and comorbidities associated with cOPLL surgery.

Results:
Of 1506 patients with cOPLL with a median of 1.8 years of follow-up after initial cOPLL diagnosis, 439 (29.2%) received cOPLL surgery. The 1-year cumulative incidence (95% CI) was 26.0% (23.7–28.2). In multivariable Cox proportional regression analysis, male (hazard ratio: 1.68; 95% CI: 1.26–2.24; P < 0.001) and obesity (body mass index: ≥25) (hazard ratio: 1.45; 95% CI: 1.10–1.89; P = 0.007) were associated with an increased risk of cOPLL surgery.

Conclusions:
In this large claims-based study of adults newly diagnosed with cOPLL, males and obesity were associated with a higher risk of cOPLL surgery. These findings may help clinicians to predict the future course of cOPLL in patients, although further research is needed to elucidate the biological role of these progression-associated factors.
Medial Locking Plate Can Increase the Fixation Stability of Vertical Femoral Neck Fracture in Young Adults?
Authors: Zanardi Vinícius Vieira , Guimarães João Antonio Matheus , Möller João Victor da Silveira , Roesler Carlos Rodrigo de Mello 
Published: February 2023

Introduction:
Vertical femoral neck fractures in young adults are usually caused by high-energy trauma. These injuries are difficult to stabilize due to significant shear forces acting on the fracture site. Their treatment is challenging and with high risks of complications, such as fixation failure, malunion, nonunion, and avascular necrosis of the femoral head.

Material and Methods:
It compared the biomechanical stability provided by 3 different fixation methods: (1) dynamic hip screw with derotation screw, (2) cannulated screws with a conventional medial bone plate, and (3) cannulated screws with a locked medial bone plate. These fixation structures were applied on fourth-generation medium-sized synthetic bones, with a 17 pound per cubic foot cellular foam core and cervico-diaphyseal angle of 120 degrees were used. The comparison was performed through biomechanical tests under cyclic loading followed by an ultimate load. The interfragmentary movement at the fracture site was the main variable for the cyclical phase.

Results:
The biomechanical comparison showed no statistical differences (P > 0.05) in stiffness, micromovement level, and mechanical resistance among the fixation techniques evaluated.

Discussion:
To stabilize the vertical femoral neck fracture in young patients, the use of a medial bone plate associated with cannulated screws on a “tie-rod” assembly is an option that supports the mechanical demand until the fracture healing. The locked medial plate did not provide an advantage compared with the conventional bone plate.
Analysis of Wholesale Drug Acquisition and Laboratory Assessment Costs Between Heparin Compared With Bivalirudin-Based Systemic Anticoagulation Strategies in Adult Extracorporeal Membrane Oxygenation
Authors: Seelhammer Troy G. , Brokmeier Hannah M. , Hamzah Mohammed , Wieruszewski Patrick M. 
Published: February 2023

OBJECTIVES:
To assess the wholistic costs of systemic anticoagulation delivery in heparin versus bivalirudin-based maintenance of adult patients supported on extracorporeal membrane oxygenation (ECMO).

DESIGN:
Single-center retrospective cohort study.

SETTING:
Large academic ECMO center.

PATIENTS:
Adults on ECMO receiving heparin or bivalirudin for primary maintenance systemic anticoagulation.

INTERVENTIONS:
None.

MEASUREMENTS AND MAIN RESULTS:
Electronic data were abstracted from a database maintained by our ECMO center, which transitioned to a preferred bivalirudin-based anticoagulation management in 2017. The pretransition group consisted of 126 patients (123 heparin and three bivalirudin), whereas the posttransition group included 275 patients (82 heparin and 193 bivalirudin). Drug costs were estimated using the wholesale acquisition cost, and laboratory assays costs were estimated using reimbursement fee schedules. Cost data were normalized to the duration of the ECMO run and reported in U.S. Dollar per ECMO day. Following the practice change, bivalirudin patients were less likely to receive AT supplementation (31.0 vs 12.4%; p < 0.0001) and had fewer coagulation assays ordered (6.1 vs 5.4 per ECMO day; p = 0.0004). After the transition, there was a dramatic decrease in costs related to AT assay assessments ($11.78 [interquartile range {IQR}, $9.48–$13.09] vs $1.03 [IQR, $0–$5.75]; p < 0.0001) and AT supplementation ($0 [IQR, $0–$312.82] vs $0 [IQR, $0–$0]; p < 0.0001) per ECMO day. Unadjusted survival at 28 days was higher posttransition (64.3 vs 74.9%; p = 0.0286).

CONCLUSIONS:
Antithrombin assays and supplementation compromise a significant proportion of heparin-based anticoagulation costs in ECMO patients and is substantially reduced when a bivalirudin-based anticoagulation strategy is deployed. A favorable association exists between the aggregate cost of administration of bivalirudin compared with heparin-based systemic anticoagulation in adults supported on ECMO driven by reductions in antithrombin activity assessments and the cost of antithrombin replacement.
Efficacy of Erbium YAG laser treatment in overactive bladder syndrome: a randomized controlled trial
Authors: Chiengthong Keerati , Bunyavejchevin Suvit 
Published: February 2023

Abstract

Objective
To evaluate the efficacy of vaginal Erbium YAG laser in postmenopausal women presenting with overactive bladder syndrome (OAB) and vaginal atrophy.

Methods
A single center, randomized sham-controlled study was conducted between July 2019 and August 2022. Thai postmenopausal women diagnosed with OAB and who complained of one or more of vaginal atrophy symptoms (VAS) were included. The participants received either one treatment session of vaginal Erbium YAG laser or the sham procedure. The primary outcome was the Thai version Overactive Bladder Symptom Score. The secondary outcomes included results from the Thai version Overactive Bladder questionnaire (OAB-q), Patient Perception of Bladder Condition Questionnaire, bladder diary, VAS score, and Vaginal Health Index score (VHI). Outcome measurements were assessed between groups at 12 weeks after treatment.

Results
Fifty participants were included and randomized. Twenty-five participants were assigned to the vaginal laser group, and 25 to the sham group. At 12-week follow-up, vaginal Erbium YAG laser demonstrated improvement compared with sham group in total Overactive Bladder Symptom Score (6.03 ± 3.36 vs 8.44 ± 3.39, P = 0.015), nocturia (1.71 ± 0.74 vs 2.32 ± 0.70, P = 0.004), and urgency (2 [3] vs 3 [4], P = 0.008). Coping and social subscale of OAB-q, daytime micturition frequency, urgency and maximum urine volume, VAS and VHI scores also significantly improved in the vaginal laser group.

Conclusions
This study showed the efficacy of the vaginal Erbium YAG laser in treatment of OAB and vaginal atrophy in postmenopausal women. The improvement of OAB symptoms scores was confirmed by the bladder diary.