Miracle-dz/UniFAR-FTUs huggingface dataset:
De novo mutations in TOMM70, a receptor of the mitochondrial import translocase, cause neurological impairment.

The Translocase of Outer Mitochondrial Membrane (TOMM) complex is the entry gate for virtually all mitochondrial proteins and is essential to build the mitochondrial proteome. TOMM70 is a receptor that assists mainly in mitochondrial protein import. Here, we report two individuals with de novo variants in the C-terminal region of TOMM70. While both individuals exhibited shared symptoms including hypotonia, hyperreflexia, ataxia, dystonia, and significant white matter abnormalities, there were differences between the two individuals, most prominently the age of symptom onset. Both individuals were undiagnosed despite extensive genetics workups. Individual 1, was found to have a p.Thr607Ile variant while individual 2 was found to have a p.Ile554Phe variant in TOMM70. To functionally assess both TOMM70 variants, we replaced the Drosophila Tom70 coding region with a Kozak-mini-GAL4 transgene using CRISPR-Cas9. Homozygous mutant animals die as pupae, but lethality is rescued by the mini-GAL4 driven expression of human UAS-TOMM70 cDNA. Both modeled variants lead to significantly less rescue indicating that they are loss-of-function alleles. Similarly, RNAi-mediated knock-down of Tom70 in the developing eye causes roughening and synaptic transmission defect, common findings in neurodegenerative and mitochondrial disorders. These phenotypes were rescued by the reference, but not the variants, of TOMM70. Altogether, our data indicate that de novo loss-of-function variants in TOMM70 result in variable white matter disease and neurological phenotypes in affected individuals.
Increased allocation to reproduction reduces future competitive ability in a burying beetle.

The existence of a trade-off between current and future reproduction is a fundamental prediction of life-history theory. Support for this prediction comes from brood size manipulations, showing that caring for enlarged broods often reduces the parent's future survival or fecundity. However, in many species, individuals must invest in competing for the resources required for future reproduction. Thus, a neglected aspect of this trade-off is that increased allocation to current reproduction may reduce an individual's future competitive ability. We tested this prediction in the burying beetle, Nicrophorus vespilloides, a species where parents care for their offspring and where there is fierce competition for resources used for breeding. We manipulated reproductive effort by providing females with either a small brood of 10 larvae or a large brood of 40 larvae and compared the ability of these females, and virgin females that had no prior access to a carcass, to compete for a second carcass against a virgin competitor. We found that increased allocation to current reproduction reduced future competitive ability, as females that had cared for a small brood were more successful when competing for a second carcass against a virgin competitor than females that had cared for a large brood. In addition, the costs of reproduction were offset by the benefits of feeding from the carcass during an initial breeding attempt, as females that had cared for a small brood were better competitors than virgin females that had no prior access to a carcass, whilst females that had cared for a large brood were similar in competitive ability to virgin females. Our results add to our understanding of the trade-off between current and future reproduction by showing that this trade-off can manifest through differences in future competitive ability and that direct benefits of reproduction can offset some of these costs.
Minimally Invasive Transforaminal Lumbar Interbody Fusion: Comparison of Grade I Versus Grade II Isthmic Spondylolisthesis

ABSTRACT Background: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is often used to treat low-grade isthmic spondylolisthesis (IS). No studies have compared surgical outcomes for grade I and II IS following MIS-TLIF. Therefore, the objective of the current study was to compare outcomes between patients with grade I and II IS following MIS-TLIF. Methods: A retrospective cohort analysis was performed on a prospectively maintained database of patients who underwent a primary 1-level MIS-TLIF for treatment of IS between 2007 and 2015. Grade I patients underwent a unilateral tubular approach with a single interbody cage and bilateral pedicle screw instrumentation. Grade II patients underwent a bilateral tubular approach with bilateral interbody cage and pedicle screw placement. Baseline patient demographics and characteristics were compared using Student t test and χ2 analysis. Differences in peri- and postoperative outcomes were assessed using Poisson regression with robust error variance or linear regression adjusted for perioperative variables. Results: A total of 58 patients with IS underwent MIS-TLIF; 21 (36.2%) were grade I and 37 (63.8%) were grade II. The grade I cohort was younger (42.2 versus 50.6 years, P = .029); no other differences in preoperative variables were observed. No significant differences in operative time, estimated blood loss, length of hospital stay, postoperative visual analogue scale scores, or complication and revision rates were demonstrated between cohorts. Arthrodesis rate was lower in the grade I cohort, though not statistically significant. Conclusions: Despite the grade I cohort being younger with less-severe diagnoses, the grade II cohort experienced similar outcomes. This finding may be due to the grade II cohort receiving bilateral cages, potentially providing a better fusion environment. Clinical Relevance: These results suggest that MIS-TLIF provides sufficient stabilization and fusion for treatment of grade II IS despite increased vertebral body displacement. In addition, MIS-TLIF with bilateral approach and interbody cage placement should be examined for treatment of high-grade IS cases.
Phosphorus quota and the chlorophyll: carbon ratio in marine phytoplankton1

From work on nutrient limited algal growth an equation was derived relating algal chlorophyll:carbon ratio ( CCI) to cell nutrient quota (Q). ccr = ccrlllax [(1-7c’,/Q)+(r/~‘,,,)l where r/$n,an is a constant representing the ratio of specific respiration rate to maximum specific growth rate, k’ & is an ( apparent ) subsistence quota, and ccrnlax is a third constant -the value of the Chl:C ratio when Q/i? * = $,,T during the period of decline the respective values of these constants were 0.0062-and 0.040. Droop ( 1968, 1970,1973) has shown that the specific growth rate of algal populations in culture is a function of the nutrient content of the cells. Taking growth to be gross photosynthesis (a) less respiration (r), specific growth rate ( p) can be described by the equation:
Giant thermopower of ionic gelatin near room temperature

Improving ionic thermoelectrics Using ions as charge carriers in thermoelectric devices usually requires using either thermal diffusion or redox reactions at two electrodes with different temperatures. Han et al. leveraged both of these strategies to develop a gelatin-based ionic thermoelectric device that uses alkali salts and an iron-based redox couple to generate a large thermopower. This device is capable of generating useful amounts of energy from body heat. Science, this issue p. 1091 A gelatin-based ionic thermoelectric material has high thermopower for conversion of body heat to energy. Harvesting heat from the environment into electricity has the potential to power Internet-of-things (IoT) sensors, freeing them from cables or batteries and thus making them especially useful for wearable devices. We demonstrate a giant positive thermopower of 17.0 millivolts per degree Kelvin in a flexible, quasi-solid-state, ionic thermoelectric material using synergistic thermodiffusion and thermogalvanic effects. The ionic thermoelectric material is a gelatin matrix modulated with ion providers (KCl, NaCl, and KNO3) for thermodiffusion effect and a redox couple [Fe(CN)64–/Fe(CN)63–] for thermogalvanic effect. A proof-of-concept wearable device consisting of 25 unipolar elements generated more than 2 volts and a peak power of 5 microwatts using body heat. This ionic gelatin shows promise for environmental heat-to-electric energy conversion using ions as energy carriers.
Thoracolumbar Dorsal Ramus Nerve Block Using Continuous Multiorifice Infusion Catheters: A Novel Technique for Postoperative Analgesia After Scoliosis Surgery

ABSTRACT Background: This is a brief technical report about a novel regional anesthesia technique in which local anesthetic was deposited around the thoracolumbar dorsal rami nerves via 4 multiorifice pain catheters to obtain analgesia for posterior spinal fusion surgery on scoliosis patients. Scoliosis is the most common deformity of the spine. Currently, most surgeons prefer a dual rod, segmental spinal fixation system that allows multiple anchor points for attachment to the deformed spine. Scoliosis surgery is an extremely painful surgical procedure due to the large incision, surgical trauma to superficial and deep muscles of the back, and the insertion of pedicle screws and metal rods directly into the vertebral column. Postoperative pain management remains very challenging. Methods: Three patients presented with scoliosis. Intraoperatively, 4 multiorifice catheters were placed lateral to the implanted pedicle screws. Two catheters were placed on each side, and a continuous infusion of 0.2 % ropivacaine was initiated postoperatively to improve the patient's pain control. The catheters remained in place for 48 hours postoperatively and were removed by the surgical team. Gentle traction was applied similar to the way epidural catheters are removed. Results: All 3 patients reported very low pain scores, low doses of opioid consumption, and satisfaction with their pain control throughout their hospitalization. Conclusions: Our study results suggest that a thoracolumbar dorsal ramus nerve block using continuous multiorifice infusion catheters significantly improved postoperative comfort and pain and that its implementation into a multimodal analgesic regimen is relatively easy to achieve.
Geographic cohesiveness versus associations with habitat: genetic subdivision of Bembicium vittatum Philippi (Gastropoda: Littorinidae) in the Houtman Abrolhos Islands

Abstract The littorine snail Bembicium vittatum has direct development and associated high levels of genetic subdivision. In the Houtman Abrolhos Islands, Western Australia, this species occupies a wide range of habitats. Replication of habitat types across the three major groups of islands, which are separated by water gaps of 10 to 15 km, separates patterns of genetic divergence related to gene flow from those expected from localised selection related to habitat. Allozyme frequencies at 14 loci were examined in samples of B. vittatum from 81 sites in the Abrolhos archipelago, at 72 of which descriptions of the physical and biological characteristics were made. Although shell shape and population density of B. vittatum varied with habitat, none of the allozymes showed such associations. Instead, there was spatial coherence of the allozyme variation, indicating connections among populations at two levels. On a larger scale, nearly half the interpopulation diversity was due to differences between island groups, including the association of rare alleles with island group. At a smaller scale, variation within island groups showed coherence in the form of isolation by distance, the extent and intensity of which were related to expected patterns of gene flow. This spatial coherence, independent of the mosaic of habitats, strongly favours the interpretation of patterns of genetic subdivision in B. vittatum in the Houtman Abrolhos as reflecting primarily the patterns of past and present gene flow. Contrasts with some results of an earlier study emphasise the importance of adequate sampling of sites and polymorphic loci.
Antibiotic-in-cyclodextrin-in-liposomes: formulation development and interactions with model bacterial membranes.

Gram-negative bacteria possess numerous defenses against antibiotics, due to the intrinsic permeability barrier of their outer membrane, explaining the recalcitrance of some common and life-threatening infections. We report the formulation of a new drug, PPA148, which shows promising activity against all Gram-negative bacteria included in the ESKAPEE pathogens. PPA148 was solubilized by inclusion complexation with cyclodextrin followed by encapsulation in liposomes. The complex and liposomal formulation presented increased activity against E. coli compared to the pure drug when assessed with the Kirby Bauer assay. The novel formulation containing 1 μg PPA148 reached similar efficacy levels equivalent to those of 30 μg pure rifampicin. A range of biophysical techniques was used to explore the mechanism of drug uptake. Langmuir trough (LT) and neutron reflectivity (NR) techniques were employed to monitor the interaction between the drug and the formulation with model membranes. We found evidence for fluidosome fusion with the model Gram-negative outer membrane and for cyclodextrins acting as inner membrane permeation enhancers without presenting intrinsic antimicrobial activity. An antibiotic-in-cyclodextrin-in-liposomes (ACL) formulation was developed, which targets both the bacterial OM and IM, and offers promise as a means to breach the Gram-negative cell envelope.
Economic evaluations considering costs and outcomes of diabetic foot ulcer infections: A systematic review

Background Diabetic foot ulcer (DFU) is a severe complication of diabetes and particularly susceptible to infection. DFU infection intervention efficacy is declining due to antimicrobial resistance and a systematic review of economic evaluations considering their economic feasibility is timely and required. Aim To obtain and critically appraise all available full economic evaluations jointly considering costs and outcomes of infected DFUs. Methods A literature search was conducted across MedLine, CINAHL, Scopus and Cochrane Database seeking evaluations published from inception to 2019 using specific key concepts. Eligibility criteria were defined to guide study selection. Articles were identified by screening of titles and abstracts, followed by a full-text review before inclusion. We identified 352 papers that report economic analysis of the costs and outcomes of interventions aimed at diabetic foot ulcer infections. Key characteristics of eligible economic evaluations were extracted, and their quality assessed against the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results 542 records were screened and 39 full-texts assessed for eligibility. A total of 19 papers were included in the final analysis. All studies except one identified cost-saving or cost-effective interventions. The evaluations included in the final analysis were so heterogeneous that comparison of them was not possible. All studies were of “excellent”, “very good” or “good” quality when assessed against the CHEERS checklist. Conclusions Consistent identification of cost-effective and cost-saving interventions may help to reduce the DFU healthcare burden. Future research should involve clinical implementation of interventions with parallel economic evaluation rather than model-based evaluations.
Relações entre a câmara de Neubauer a espectrofotometria utilizadas para a determinação da concentração espermática de catetos (Pecari tajacu)

In ejaculates derived from 28 collared peccaries, we verified the existence of relationships between sperm concentration determined by the Neubauer counting chamber and the tramitance verified by spectrophotometer, under wavelengths varying from 530 to 590nm. Ejaculates presented a concentration of 283.9±30.8x106sperm m-1, varying from 30 to 640x106sperm mL-1. Values for tramitance varied from 36.9 to 96.3, under different wavelengths. No significant relationship was verified between two methods (P>0.05). Thus, the spectrophotometer is not recommended for routine procedures of sperm concentration measurement in collared peccaries.
Exploring the knowledge and attitudes of Cameroonian medical students towards global surgery: A web-based survey

Introduction Global surgery is a growing field studying the determinants of safe and affordable surgical care and advocating to gain the global health community's attention. In Cameroon, little is known about the level of knowledge and attitudes of students. Our survey aimed to describe the knowledge and attitudes of Cameroonian medical students towards global surgery. Materials and methods We performed an anonymous online survey of final-year Cameroonian medical students. Mann-Whitney U test and Spearman correlation analysis were used for bivariate analysis, and the alpha value was set at 0.05. Odds ratios and their 95% confidence intervals were calculated. Results 204 respondents with a mean age of 24.7 years (±2.0) participated in this study. 58.3% were male, 41.6% had previously heard or read about global surgery, 36.3% had taken part in a global surgery study, and 10.8% had attended a global surgery event. Mercy Ships was well known (46.5%), and most students believed that surgical interventions were more costly than medical treatments (75.0%). The mean score of the global surgery evaluation was 47.4% (±29.6%), and being able to recognize more global surgery organizations was correlated with having assumed multiple roles during global surgery studies (p = 0.008) and identifying more global surgery indicators (p = 0.04). Workforce, infrastructure, and funding were highlighted as the top priorities for the development of global surgery in Cameroon. Conclusion Medical students are conscious of the importance of surgical care. They lack the opportunities to nurture their interest and should be taught global surgery concepts and skills.
Are Pathogenic Germline Variants in Metastatic Melanoma Associated with Resistance to Combined Immunotherapy?

Background: Combined immunotherapy has significantly improved survival of patients with advanced melanoma, but there are still patients that do not benefit from it. Early biomarkers that indicate potential resistance would be highly relevant for these patients. Methods: We comprehensively analyzed tumor and blood samples from patients with advanced melanoma, treated with combined immunotherapy and performed descriptive and survival analysis. Results: Fifty-nine patients with a median follow-up of 13 months (inter quartile range (IQR) 11–15) were included. Interestingly, nine patients were found to have pathogenic or likely pathogenic (P/LP) germline variants in one of these genes: BRCA2, POLE, WRN, FANCI, CDKN2A, BAP1, PALB2 and RAD54B. Most of them are involved in DNA repair mechanisms. Patients with P/LP germline variants had a significantly shorter progression-free survival (PFS) and melanoma specific survival (MSS) compared to patients without P/LP germline variants (HR = 2.16; 95% CI: 1.01–4.64; p = 0.048 and HR = 3.21; 95% CI: 1.31–7.87; p = 0.011, respectively). None of the patients with a P/LP germline variant responded to combined immunotherapy. In the multivariate Cox-regression analysis, presence of a P/LP germline variant, S100B and lactate dehydrogenase (LDH) remained independently significant factors for MSS (p = 0.036; p = 0.044 and p = 0.001, respectively). Conclusions: The presence of P/LP germline variants was associated with resistance to combined immunotherapy in our cohort. As genes involved in DNA repair mechanisms are also involved in lymphocyte development and T-cell differentiation, a P/LP germline variant in these genes may preclude an antitumor immune response.
Enhancing Performance of Stretchable and Transparent Triboelectric Nanogenerator by Optimizing Hydrogel Ionic Electrode Property.

Triboelectric nanogenerators (TENGs) with high transparency and stretchability are desired for invisible and adaptable energy harvesting and sensing. Hydrogel-based TENGs (H-TENG) have shown promising attributes towards flexible and transparent devices. However, the effect of hydrogel property on the triboelectric performance of H-TENG is rarely investigated. Herein, dual-network hydrogels composed of dual-crosslinked polyvinyl alcohol (PVA) and sodium alginate (SA) were synthesized and used as ionic electrodes in H-TENGs. The elasticity of the hydrogel was controlled by varying the concentration of SA, and the distinct influence of hydrogel viscoelastic property on H-TENG performance was verified for the first time. The optimum H-TENG was fabricated by tuning the conductivity and viscoelasticity of PVA/SA hydrogel. The optimum H-TENG possesses high transparency (over 90%) and stretchability (over 250%), and peak output voltage and current of 203.4 V and 17.6 µA, respectively. Specially designed polydimethylsiloxane (PDMS) bag effectively prevents hydrogel dehydration and maintain a stable output in continuous operation. The H-TENG achieved a power density of 0.98 W/m2 on a 4.7 MΩ external resistor. The H-TENG could easily light 240 green and blue LEDs simultaneously, and demonstrated capability to power small electronics, such as a digital timer and pedometer. This study provides insights into the influence of hydrogel property on H-TENG performance and gives guidance for designing and fabrication of highly stretchable and transparent TENGs.
Investigation of the human nasal microbiome in persons with long- and short-term exposure to methicillin-resistant Staphylococcus aureus and other bacteria from the pig farm environment

Since its emergence in the early 2000s, livestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398) has led to an increasing number of human infections in Denmark and other European countries with industrial pig production. LA-MRSA CC398 is primarily associated with skin infections among pig farm workers but is also increasingly recognized as a cause of life-threatening disease among elderly and immunocompromised people. Pig farm workers may serve as vehicles for the spread of LA-MRSA CC398 and other farm-origin bacteria between farms and into the general population. Yet, little is known about the bacterial community dynamics in pig farm workers and other persons with long- and short-term exposure to the pig farm environment. To gain insight into this, we investigated the nasal microbiomes in pig farm workers during a workweek on four LA-MRSA CC398-positive pig farms, as well as in short-term visitors two hours before, immediately after, and 48 hours after a 1-hour visit to another LA-MRSA CC398-positive pig farm. S. aureus and LA-MRSA CC398 carriage was quantified by means of culture, and the composition of the bacterial communities was investigated through sequencing of the 16S rRNA gene. Pig farm workers often carried LA-MRSA CC398 and other bacteria from the pig farm environment, both at work and at home, although at lower levels at home. In contrast, short-term visitors were subject to a less dramatic and rapidly reversible change in the nasal bacterial community composition. These results suggest that pig farm workers may be an important source of LA-MRSA CC398 and perhaps other pathogens of human and veterinary relevance.