Miracle-dz/UniFAR-FTUs huggingface dataset:
Excessive CD11c+Tbet+ B cells promote aberrant TFH differentiation and affinity-based germinal center selection in lupus

Significance The paradoxical coexistence of excessive autoantibodies and inadequate affinity-matured pathogen-specific antibodies in lupus is poorly understood. Here, we found that excessive CD11c+T-bet+ age-associated B cells (ABCs)—a recently described autoimmunity-relevant B cell subset [K. Rubtsova et al., J. Clin. Invest. 127, 1392–1404 (2017)]—not only contribute to the production of autoantibodies but also promote aberrant follicular T-helper (TFH) cell differentiation and consequently compromise affinity-based germinal center (GC) B-cell selection and antibody-affinity maturation in lupus mouse models. Importantly, ablating B cell-intrinsic Toll-like receptor (TLR) signaling adaptor MyD88 in lupus mice inhibited CD11c+T-bet+ ABC differentiation, normalized TFH differentiation, and rescued GC selection, as well as prevented autoantibody production, suggesting that CD11c+T-bet+ ABCs and TLR signaling are potential targets for lupus treatment. Excessive self-reactive and inadequate affinity-matured antigen-specific antibody responses have been reported to coexist in lupus, with elusive cellular and molecular mechanisms. Here, we report that the antigen-specific germinal center (GC) response―a process critical for antibody affinity maturation―is compromised in murine lupus models. Importantly, this defect can be triggered by excessive autoimmunity-relevant CD11c+Tbet+ age-associated B cells (ABCs). In B cell-intrinsic Ship-deficient (ShipΔB) lupus mice, excessive CD11c+Tbet+ ABCs induce deregulated follicular T-helper (TFH) cell differentiation through their potent antigen-presenting function and consequently compromise affinity-based GC selection. Excessive CD11c+Tbet+ ABCs and deregulated TFH cell are also present in other lupus models and patients. Further, over-activated Toll-like receptor signaling in Ship-deficient B cells is critical for CD11c+Tbet+ ABC differentiation, and blocking CD11c+Tbet+ ABC differentiation in ShipΔB mice by ablating MyD88 normalizes TFH cell differentiation and rescues antigen-specific GC responses, as well as prevents autoantibody production. Our study suggests that excessive CD11c+Tbet+ ABCs not only contribute significantly to autoantibody production but also compromise antigen-specific GC B-cell responses and antibody-affinity maturation, providing a cellular link between the coexisting autoantibodies and inadequate affinity-matured antigen-specific antibodies in lupus models and a potential target for treating lupus.
Comparing Nipple-sparing Mastectomy to Secondary Nipple Reconstruction

Supplemental Digital Content is available in the text Objective: The primary aim of this study was to compare patient-reported outcomes (PROs) of women who underwent immediate implant-based breast reconstruction (IBBR) after receiving either: (1) nipple-sparing mastectomy (NSM) or (2) simple mastectomy with subsequent nipple reconstruction (SNR). Background: The goal of post-mastectomy breast reconstruction is to restore body image and quality-of-life after mastectomy, but removal of the nipple-areolar complex may have its own negative psychosocial consequences. NSM may have increased in popularity due to its perceived oncologic safety in many women and to reports of superior aesthetic results with this technique. Despite the increased utilization of NSM, few studies have evaluated the impact of NSM on PROs and complications in women undergoing immediate IBBR. Methods: We performed a secondary analysis of the Mastectomy Reconstruction Outcomes Consortium study, a multicenter, prospective cohort study that recruited patients between February 2012 and July 2015. The primary aim of this study was to compare PROs as measured by BREAST-Q scores between women who underwent IBBR after NSM versus SNR. The secondary aim was to compare complication rates. Mixed-effects regression models controlled for demographic and clinical covariates. Results: Of the 600 women in the study, 286 (47.7%) underwent NSM. After controlling for baseline patient characteristics, we found no significant differences in satisfaction with breast, psychosocial well-being, physical well-being or sexual well-being between women undergoing NSM versus SNR. Mastectomy type was not a significant predictor of complications or reconstructive failure. Conclusions: Despite reports of superior aesthetics for NSM over simple mastectomy with nipple reconstruction in immediate IBBR, we found no significant differences at 2 years after reconstruction in patient satisfaction, quality-of-life, or complication rates.
Attitudes of editors of core clinical journals about whether systematic reviews are original research: a mixed-methods study

Objectives In 2009, not all journal editors considered systematic reviews (SRs) to be original research studies, and not all PubMed Core Clinical Journals published SRs. The aim of this study was to conduct a new analysis about editors’ opinion regarding SRs as original research. Design We conducted a survey and qualitative interview study of journal editors. Participants All editors listed as editor-in chief of 118 PubMed Core Clinical Journals. Methods We contacted editors via email and asked them whether they considered SRs original research, whether they published SRs in the journal and, if yes, in which section. We searched PubMed for any SRs (or meta-analyses) published in the included journals in 2017; if we did not find any, we hand-searched these journals. Editors were invited to participate in a follow-up qualitative interview study. Results We received responses from 73 editors representing 72 (62%) journals. Fifty-two (80%) editors considered SRs original research, either for any type of SR (65%) or only for SRs with a meta-analysis (15%) and almost all (91%) of editors published SRs. Compared with the results of the 2009 study of Core Clinical Journals, a similar proportion of editors considered SRs to be original studies (71%), accepted SRs as original on certain condition such as presence of meta-analysis (14%) or published SRs (94%). Interviews with editors showed that they used various criteria to decide whether a SR is original research, including methodology, reproducibility, originality of idea and level of novelty. Conclusion The majority of editors of core clinical journals consider that SRs are original research. Among editors, there was no uniform approach to defining what makes a SR, or any study, original. This indicates that the concepts of originality of SRs and research are evolving and that this would be a relevant topic for further discussion.
Impact of CBCT on treatment decision related to surgical removal of impacted maxillary third molars: does CBCT change the surgical approach?

OBJECTIVES To assess factors influencing treatment decision for maxillary third molars referred for cone beam CT (CBCT). Parameters influencing the decision to treat and to remove either the maxillary second molar or third molar were pursued. METHODS 111 impacted maxillary third molars, clinically examined including a panoramic image, in 86 patients (mean age 26 years, range 15-55) were referred for CBCT on suspicion of pathology/root resorption in the second molar, based on information in the panoramic image. The following parameters were assessed from the patient's file, including the radiographic images: (1) third molar angulation; (2) initial treatment plan based on clinical examination and the panoramic image; (3) diagnoses based on information from CBCT; (4) treatment decision after additional CBCT information was available; (5) pre-/post-operative complications; (6) treatment of the maxillary second molar. RESULTS 70 cases (63.1%) underwent treatment, while 41 (36.9%) received no treatment. Change in treatment plan was registered in 65 cases (58.6%) after CBCT. In 12 cases (10.8%), treatment changed from removal of the third to removal of the second molar, while 25 (22.5%) were scheduled for removal in the initial treatment plan; but after CBCT, the decision was not to treat. If external root resorption involved the pulp of the second molar, there was an almost 17 times higher risk that this tooth was removed instead of the third molar (logistic regression analysis: odds ratio 16.8; p < 0.001). CONCLUSIONS Findings in CBCT often changed the treatment plan. Severe external root resorption observed in CBCT was the main decisive factor for removing the second instead of the third molar.
Hypertension and chronic kidney disease is highly prevalent in elderly patients with colorectal cancer undergoing primary surgery.

BACKGROUND Colorectal cancer (CRC) is a common and lethal disease. Hypertension is the most commonly reported comorbidity among cancer patients. Data on its incidence and prevalence is very scarce. OBJECTIVES The aim of the study was to evaluate the prevalence of hypertension and chronic kidney disease (CKD) in a cohort of 100 consecutive patients with CRC undergoing primary surgical treatment. MATERIAL AND METHODS The pilot study included 100 consecutive patients with CRC undergoing primary surgery with curative intent within 1 year in the Department of Oncological Surgery in Białystok, Poland. No neoadjuvant therapy was administered before the surgery. RESULTS The prevalence of hypertension was 62% among the patients studied. Sixty-five percent of the patients were older than 65 years and hypertension was present in 78% of these elderly patients. The prevalence of CKD was 15%, while that of diabetes was 23%. All CKD patients were older than 65 years of age. The hypertensive patients were more likely to be older and anemic with higher serum fibrinogen, which reflects a general inflammatory state. Elderly hypertensive patients had significantly higher creatinine levels, lower estimated glomerular filtration rate (eGFR) levels (p < 0.001) and lower platelet counts. CONCLUSIONS It is of the utmost importance for oncology patients to have any hypertension diagnosed and treated appropriately in order to prevent complications so they may continue their therapy with the least interruption or discontinuation of treatment and to ensure the best possible outcomes.
Periprosthetic Joint Infection Caused by Gram-Positive Versus Gram-Negative Bacteria: Lipopolysaccharide, but not Lipoteichoic Acid, Exerts Adverse Osteoclast-Mediated Effects on the Bone

Periprosthetic joint infection (PJI)—the most common cause of knee arthroplasty failure—may result from Gram-positive (GP) or Gram-negative (GN) bacterial infections. The question as to whether PJI due to GP or GN bacteria can lead to different rates of aseptic loosening after reimplantation remains open. We have investigated this issue through a retrospective review of clinical records obtained from 320 patients with bacterial PJI. The results revealed that, compared with GP infections, GN infections were associated with an increased risk of aseptic loosening. In animal studies, mice underwent intrafemoral injection of lipopolysaccharide (LPS) from GN bacteria or lipoteichoic acid (LTA) from GP bacteria. We demonstrate that LPS—but not LTA—reduced both the number of trabeculae and the bone mineral density in mice. In addition, LPS-treated mice exhibited a reduced body weight, higher serum osteocalcin levels, and an increased number of osteoclasts. LPS accelerated monocyte differentiation into osteoclast-like cells, whereas LTA did not. Finally, ibudilast—a toll-like receptor (TLR)-4 antagonist—was found to inhibit LPS-induced bone loss and osteoclast activation in mice. Taken together, our data indicate that PJI caused by GN bacteria portends a higher risk of aseptic loosening after reimplantation, mainly because of LPS-mediated effects on osteoclast differentiation.
Microvesicle-Mediated Delivery of Minicircle DNA Results in Effective Gene-Directed Enzyme Prodrug Cancer Therapy

An emerging approach for cancer treatment employs the use of extracellular vesicles, specifically exosomes and microvesicles, as delivery vehicles. We previously demonstrated that microvesicles can functionally deliver plasmid DNA to cells and showed that plasmid size and sequence, in part, determine the delivery efficiency. In this study, delivery vehicles comprised of microvesicles loaded with engineered minicircle (MC) DNA that encodes prodrug converting enzymes developed as a cancer therapy in mammary carcinoma models. We demonstrated that MCs can be loaded into shed microvesicles with greater efficiency than their parental plasmid counterparts and that microvesicle-mediated MC delivery led to significantly higher and more prolonged transgene expression in recipient cells than microvesicles loaded with the parental plasmid. Microvesicles loaded with MCs encoding a thymidine kinase (TK)/nitroreductase (NTR) fusion protein produced prolonged TK-NTR expression in mammary carcinoma cells. In vivo delivery of TK-NTR and administration of prodrugs led to the effective killing of both targeted cells and surrounding tumor cells via TK-NTR–mediated conversion of codelivered prodrugs into active cytotoxic agents. In vivo evaluation of the bystander effect in mouse models demonstrated that for effective therapy, at least 1% of tumor cells need to be delivered with TK-NTR–encoding MCs. These results suggest that MC delivery via microvesicles can mediate gene transfer to an extent that enables effective prodrug conversion and tumor cell death such that it comprises a promising approach to cancer therapy.
Relationship Between Bench Press Strength and Punch Performance in Male Professional Boxers.

López-Laval, I, Sitko, S, Muñiz-Pardos, B, Cirer-Sastre, R, and Calleja-González, J. Relationship between bench press strength and punch performance in male professional boxers. J Strength Cond Res XX(X): 000-000, 2019-This study investigated the relationship between punching performance and the velocity at which different loads were lifted during the bench press (BP) exercise in 12 professional boxers (age = 22.6 ± 4 years; height = 177.7 ± 5 cm; body mass 70.6 ± 6.43 kg; years of boxing experience = 6.5 ± 3.5 years; weight class = from light to super welterweight). To determine the maximal punching velocity (PVmax) during both rear arm (RA) and lead arm (LA) punching, an accelerometer (Crossbow; Willow Technologies, Sussex, United Kingdom) was placed inside the boxing glove while executing 3 jaws at a maximal velocity with each arm. Upper-body strength was assessed through the direct 1-repetition maximum (1RM) BP test, and the maximum velocity at different percentages of 1RM was obtained with a linear encoder. The main finding was that RA PVmax was correlated with the BP velocity at all submaximal intensities (p < 0.05). Nevertheless, LA PVmax did not correlate with BP velocity at any intensity. When the correlated BP submaximal intensities were introduced in linear regression models, the velocity at 80% 1RM was the only predictor of RA PVmax (r = 0.75; p < 0.01) in professional boxers. Additional body mass adjustment to the regression model significantly affected the predictive value (r = 0.65; p < 0.005). Results encourage coaches and trainers to use BP exercise with high loads (i.e., 80% of 1RM) because this could be a reliable predictor of performance during the specific boxing action. Future research is needed to determine exercises and intensities that could explain LA PVmax because significant associations were not found.
SEROEPIZOOTIC SURVEY OF LEPTOSPIROSIS IN HORSES

Leptospirosis is a common infectious disease which is wide spread all over the world. 440 of blood serum samples were tested to determine the spread of this contagious disease amongst equine family animals (horses, Shetland ponies, donkeys) in Lithuania. The survey was carried out in 2011 – 2015 period, blood samples were tested by MA test. There were found that 18.63% of investigated horses are serologicaly positive for leptospirosis The highest percentage 19.6% of positive samples were from stud farms’ horses. Antibodies against serogroups of L. canicola (33.0%), L. copenhagen (26.1%) and L. grippotyphosa (20.9%) were identified in analysed samples. Most positive results (31.8%) were found among horses located in Panevezys County. Mares consisted 69.5% of all the positive reacted horses.
Semantic memory for objects, actions, and events: A novel test of event-related conceptual semantic knowledge

ABSTRACT People possess significant knowledge about how real-world events typically unfold. Such event-related semantic memory connects action and object knowledge, is essential for multiple stages of language processing, and may be impaired in neurological conditions like aphasia. However, current assessments are not well designed for measuring this knowledge. This study presents and tests a novel measure of event-related semantic memory. Task-performance data were collected from unimpaired adults across the lifespan and a sample of stroke survivors with aphasia. Individuals with aphasia also completed measures of language processing and action-/object-related semantic memory, to establish the novel measure's convergent validity. Results demonstrate that performance on the event-knowledge measure correlated with action and object semantic-memory measures and was also associated with a broader range of language-processing performance than other semantic-memory measures. These findings suggest that the novel measure can be used to detect the presence and impact of event-knowledge impairments in neurological conditions.
A Case of Conjunctival Bee Sting Injury with Review of the Literature on Ocular Bee Stings

Patient: Male, 24 Final Diagnosis: Bee sting conjunctival injury Symptoms: Eye pain • red eye Medication: — Clinical Procedure: Ablation of the bee sting Specialty: Ophthalmology Objective: Unusual clinical course Background: Ocular bee stings have been rarely described in the literature, and their management is controversial. A case of conjunctival bee sting with retention of the stinger for 48 hours is presented with a review of the literature on the complications and management of ocular bee sting injury. Case Report: A 22-year-old beekeeper presented to the Emergency Department with mild symptoms from a conjunctival bee sting that he had received 48 hours previously. The stinger was removed in the Emergency Department, and topical antibiotic and anti-inflammatory treatment with corticosteroid were given. There were no complications in this case. However, review of the literature has shown that although the outcome from ocular bee stings can be mild, as in this case, ocular bee stings can result in severe visual symptoms that require amniotic membrane transplant (AMT). Management commonly includes removal of the stinger and both topical and systemic treatment with corticosteroids. The main complications include cataracts, inflammation of the anterior chamber, optic neuropathies, and changes in ocular pressure. Conclusions: Ocular bee stings have been rarely described in the literature, and the management remains controversial. As this case has shown, removal of the stinger and the use of topical treatment with antibiotics and corticosteroids can prevent potentially serious complications that may affect vision. Early and regular follow-up with ocular imaging may be required when symptoms persist.
Combining MAP‐1:CD35 or MAP‐1:CD55 fusion proteins with pattern‐recognition molecules as novel targeted modulators of the complement cascade

Dysregulation of the complement system is involved in the pathogenesis of several diseases, and its inhibition has been shown to be a feasible therapeutic option. Therefore, there is an interest in the development of complement modulators to treat complement activation–related inflammatory pathologies. Mannose‐binding lectin (MBL)/ficolin/collectin‐associated protein‐1 (MAP‐1) is a regulatory molecule of the lectin pathway (LP), whereas complement receptor 1 (CD35) and decay‐accelerating factor (CD55) are membrane‐anchored regulators with effects on the central effector molecule C3. In this study, we developed 2 novel soluble chimeric inhibitors by fusing MAP‐1 to the 3 first domains of CD35 (CD351–3) or the 4 domains of CD55 (CD551–4) to modulate the complement cascade at 2 different stages. The constructs showed biologic properties similar to those of the parent molecules. In functional complement activation assays, the constructs were very efficient in inhibiting LP activation at the level of C3 and in the formation of terminal complement complex. This activity was enhanced when coincubated with recombinant LP recognition molecules MBL and ficolin‐3. Recombinant MAP‐1 fusion proteins, combined with recombinant LP recognition molecules to target sites of inflammation, represent a novel and effective therapeutic approach involving the initiation and the central and terminal effector functions of the complement cascade. —Pérez‐Alós, L. , Bayarri‐Olmos, R. , Skjoedt, M. ‐O. , Garred, P. Combining MAP‐1:CD35 or MAP‐1:CD55 fusion proteins with pattern‐recognition molecules as novel targeted modulators of the complement cascade. FASEB J. 33, 12723–12734 (2019). www.fasebj. org
Coinheritance of Hb A2-Melbourne (HBD: c.130G>A) and Hb E (HBB: c.79G>A) in Laos and Simultaneous High Resolution Melt Detection of Hb A2-Melbourne and Hb A2-Lampang (HBD: c.142G>A) in a Single Tube

Abstract We report the molecular and hematological identifications of a Hb A2 variant [coinheritance of Hb A2-Melbourne (HBD: c.130G>A) and Hb E (HBB: c.79G>A)] found for the first time in the Lao People’s Democratic Republic (PDR). The subject was a 29-year-old pregnant Laotian woman who was a foreign worker in Thailand and was diagnosed with thalassemia and hemoglobinopathies. Capillary electrophoresis (CE) demonstrated 1.6% of Hb A2, with a minor unknown peak at the initial Z1 zone (1.7%). Identification of abnormal hemoglobin (Hb) using direct DNA sequencing showed a genetic defect causing a δ-globin gene missense mutation at codon 43 (GAG>AAG) causing a glutamic acid to lysine substitution corresponding to Hb A2-Melbourne. The origin of Hb A2-Melbourne in Lao PDR may be similar to a case found in Thailand with the [+ – – – – + +] haplotype. We developed a method that could clearly detect Hb A2-Melbourne and Hb A2-Lampang (HBD: c.142G>A) mutations in a single tube using high resolution melt (HRM) analysis. The HRM analysis is a more effective method for rapid detection than conventional polymerase chain reaction (PCR), as there is no need for a post-PCR step, and no exposure to ethidium bromide. This new method would be a useful addition for the first investigation of a suspected Hb A2 variant in the routine molecular setting.
Design of modular gellan gum hydrogel functionalized with avidin and biotinylated adhesive ligands for cell culture applications

This article proposes the coupling of the recombinant protein avidin to the polysaccharide gellan gum to create a modular hydrogel substrate for 3D cell culture and tissue engineering. Avidin is capable of binding biotin, and thus biotinylated compounds can be tethered to the polymer network to improve cell response. The avidin is successfully conjugated to gellan gum and remains functional as shown with fluorescence titration and electrophoresis (SDS-PAGE). Self-standing hydrogels were formed using bioamines and calcium chloride, yielding long-term stability and adequate stiffness for 3D cell culture, as confirmed with compression testing. Human fibroblasts were successfully cultured within the hydrogel treated with biotinylated RGD or biotinylated fibronectin. Moreover, human bone marrow stromal cells were cultured with hydrogel treated with biotinylated RGD over 3 weeks. We demonstrate a modular and inexpensive hydrogel scaffold for cell encapsulation that can be equipped with any desired biotinylated cell ligand to accommodate a wide range of cell types.