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Abstract Transcription of human mitochondrial DNA (mtDNA) begins from specific transcription promoters. In strand-asynchronous mtDNA replication, transcripts from the light-strand promoter serve as primers for leading-strand synthesis at the origin of the H-strand replication (OH). A 7S DNA strand, a presumed aborted replication product, is also synthesized from OH. Transition from RNA synthesis to DNA synthesis at OH is crucial for balancing replication with transcription, yet the mechanism remains unclear. Herein, we examine the role of mitochondrial transcription elongation factor (TEFM) in this process. TEFM knockout results in decreased 7S DNA, strand-asynchronous replication intermediates, and mtDNA copy number, all of which are concordant with downregulation of RNA-to-DNA transition at OH. Conversely, levels of tRNAs encoded near transcription promoters increase, indicating enhanced transcription initiation frequency. Taken together, we propose that, in addition to conferring processivity to the mitochondrial RNA polymerase, TEFM plays a crucial role in maintaining the balance between mitochondrial transcription and replication.

Venetoclax and azacitidine combination therapy (VEN+AZA) is a promising novel therapy for elderly or unfit patients with acute myeloid leukemia (AML). Recently, VEN+AZA with subsequent allo-hematopoietic stem cell transplantation has been reported, and human leukocyte antigen-haploidentical peripheral blood stem cell transplantation using posttransplant cyclophosphamide (PTCy-haplo-PBSCT) from related donors appears to be a suitable option. Here, we report two elderly patients with refractory AML harboring an IDH2 mutation, who were successfully treated with VEN+AZA bridged to PTCy-haplo-PBSCT. This report suggests the efficacy and safety of VEN+AZA as a bridging treatment for PTCy-haplo-PBSCT in refractory AML.

Abstract Vibration characteristics of wood-based materials are essential parameters in considering the indoor environment of a building. This study investigates the effect of the physical properties of water-based adhesives on vibration characteristics of wood-based materials. Adhesive films and particle boards (PB) were prepared from acrylic emulsion adhesives (AE) with differential glass transition (T g), and loss tangent of dynamic viscoelasticity (tanδ D) and flexural vibration property (tanδ F) were compared. The tanδ D master curve and tanδ F showed a similar tendency regarding frequency dependence. The apparent activation energy (ΔH) calculated from the shift factor of the master curve tends to be different depending on the T g of AE and was especially high for AE with T g = 13 °C along with blended AE. The dynamic Young’s modulus (E F) calculated from the flexural vibration tests showed higher values for AE at T g = 13 °C, 41 °C, and 90 °C than that of urea–formaldehyde adhesive (UF).

The concurrent onset of chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) is rare, and no autopsy case has been reported. We report herein the first case of concurrent-onset CLL and AML with an atypical phenotype revealed by autopsy. Notably, the diagnosis of AML was quite difficult during the patient’s lifetime because of the atypical phenotype. However, autopsy revealed that the patient’s bone marrow, liver, and spleen were filled with myeloblasts. In addition, p53 stain and PCR of IgH rearrangement using the autopsy specimen suggested that CLL and AML might be different clones. In conclusion, our case highlights the importance of considering synchronous complications of AML in CLL patients, particularly in those with an atypical clinical course.

Fiddler crabs are one of the most notable animal groups in Brazilian estuarine environments, due to their high density and characteristic waving of males. An illustrated key to the ten species recorded as far in the country is provided using only clearly visible characters of males. Furthermore, additional recognition characters, information about geographic distribution and biology of each species are presented. Most examined crabs were collected in Guaratuba Bay, southern Brazil.

Abstract Venetoclax is a promising new drug for relapsed or refractory chronic lymphocytic leukemia (CLL). However, venetoclax use had not been reported in severe chronic kidney disease (CKD) patients. We report the first case of relapsed CLL in a severe CKD patient that was successfully treated with venetoclax.

Abstract The population structure and growth of two populations (Arraial and Capivari rivers) of Aegla schmitti was evaluated. The following parameters were determined: size, age structure, sex ratio, recruitment period, and sampling method selectivity (traps and handnet). There was variation between males and females. The carapace length size class distribution was unimodal in the Arraial River, and polymodal in the Capivari River. The sampling method influenced the proportion of demographic categories. The recruitment occurred mostly between October and December. The growth curves for the Arraial and Capivari rivers, respectively, were Ct= 26,50[1- e -0,004(t+53,36)] and Ct= 34,79[1- e -0,0024(t+122,34)] for males, and Ct= 23,07[1- e -0.0027(t+23,18)] and Ct= 25.52[1- e -0,0033(t+19,51)] for females. The maximum CL estimated for males and females were 26.50 and 23.07mm for the Arraial River, and 34.79 and 25.52mm for the Capivari River. Longevity was estimated in 2 years for females of both populations, and 2.5 and 3 years for males of the Arraial and Capivari rivers, respectively. The results allow for the characterization of the growth patterns of A. schmitti in two hydrographic basins, providing information for the species’ preservation and also demonstrating the selectivity of the different sampling methods used for aeglids.

# Background A forefoot strike (FFS) could be a safer landing technique than a rearfoot strike (RFS) during a cutting motion to prevent anterior cruciate ligament (ACL) injury. # Purpose This study aimed to determine the joint angles, ground reaction force (GRF), and muscle activity levels associated with FFS and RFS landings during 180° turns. # Study design Cross-sectional study # Methods Fourteen male soccer players from the University of Tsukuba football (soccer) club participated in this study. The FFS consisted of initial contact with the toes on the force plates followed by the rearfoot; meanwhile, the initial contact was performed with the heels on the force plates followed by the forefoot for the RFS. Ankle, knee, and hip joint angles were recorded using a three-dimensional motion capture system. GRFs were measured using a force plate. Gluteus medius (GM), rectus femoris (RF), vastus medialis (VM), vastus lateralis (VL), semitendinosus (ST), biceps femoris (BF), tibialis anterior (TA), and lateral gastrocnemius (GL) activities were measured by electromyography. # Results The activities of GM, GL, and ST from initial contact to early periods during landing into the ground with the FFS are larger than those with RFS. In addition, the results showed significant differences in lower-limb angles and GRFs between the FFS and RFS. # Conclusion These results suggest that there might be differences in ACL injury risk during a 180° turn between the FFS and the RFS pattern. An investigation into the grounding method that prevents injury is necessary in future studies. # Levels of Evidence Level 3b

Introduction Crustaceans have multiple thoracic appendages, called pereiopods. In many species of decapod crustaceans, the two distal segments (dactylus and propodus) of the most anterior pereiopods form a claw, called [...], The paired claws in Gazami crabs, Portunus trituberculatus, are bilaterally asymmetrical, and asymmetry is remarkable on the distal two segments of the first pereiopod, that is, the dactylus and propodus. Shells are exclusively cracked by use of the right chela, representing handedness. In Gazami crabs, handedness is reversed after autotomy of the right chela. Our study focused on the ontogeny of handedness and the mechanism of handedness reversal. Morphologically, asymmetry was first detected in megalopa larvae where the right propodus was significantly larger than the left, as was the canine at the base of the right dactylus. Presumably, the rate of chelagenesis differed between the left and right chelae. With these morphological features, the right chela functioned as a crusher. The crusher exerted a closing force two to three times that of the cutter. With loss of the right crusher, the left chela was bigger than the regenerated right chela and was converted to the crusher. In contrast, the performance of the regenerated right chela deteriorated compared to that of the original right crusher, and exertion of full closing force was inhibited by the more active left chela. Furthermore, crabs with two crusher chelae did not clearly show handedness. A decrease in size and performance of the regenerated right chela can be explained by a default program hypothesis. In conclusion, a difference in the chelagenesis rate results in bilateral asymmetry of the two chelipeds, and then handedness is generated by neural regulation in the thoracic ganglion innervating these claws. Since handedness is reversed after autotomy, the thoracic ganglion would not be lateralized in Gazami crabs. A default program hypothesis is proposed to explain the ontogeny of bilateral chela asymmetry and handedness reversal.

Abstract The influence of salinity on the survival of the larvae of Leptuca leptodactyla (Rathbun, in Rankin, 1898) from zoea (Z) to megalopa (M) stage was analyzed in order to deduce the larval dispersal strategy of the species. Larvae were obtained from 10 ovigerous females captured in the mangrove of Guaratuba Bay, southern Brazil. Five salinity treatments were conducted from 0 to 35 PSU (S0, S5, S15, S25 and S35). The larvae were individually raised in plastic cell culture plates, totaling 120 experimental units per treatment, kept under natural photoperiod (12:12 h) and water constant temperature (26.3 ± 0.82°C), and fed with microalgae, rotifers and Artemia nauplii. While all larvae died at S0, S5 and S15, complete larval development until the M stage was only observed at S25 and S35. The highest survival rate was recorded at S35 (18 M from 120 newly-hatched Z, survivorship 15%) and the lowest at S25 (2 M, 1.66%). No significant difference in the total duration was observed between S25 (28.5 ± 0.70 days) and S35 (23.61 ± 3.05 days). The life cycle of L. leptodactyla is based on a larval exportation strategy as they need to perform ontogenetic migrations to the coastal area.

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Background: Only few studies have investigated the relationship between the histopathology of retrieved thrombi and clinical outcomes. This study aimed to evaluate thrombus composition and its association with clinical, laboratory, and neurointerventional findings in patients treated by mechanical thrombectomy due to acute large vessel occlusion. Methods: At our institution, 79 patients were treated by mechanical thrombectomy using a stent retriever and/or aspiration catheter between August 2015 and August 2016. The retrieved thrombi were quantitatively analyzed to quantify red blood cells, white blood cells, and fibrin by area. We divided the patients into two groups – a fibrin-rich group and an erythrocyte-rich group – based on the predominant composition in the thrombus. The groups were compared for imaging, clinical, and neurointerventional data. Results: The retrieved thrombi from 43 patients with acute stroke from internal carotid artery, middle cerebral artery, or basilar artery occlusion were histologically analyzed. Erythrocyte-rich thrombi were present in 18 cases, while fibrin-rich thrombi were present in 25 cases. A cardioembolic etiology was significantly more prevalent among the patients with fibrin-rich thrombi than among those with erythrocyte-rich thrombi. Attenuation of thrombus density as shown on computed tomography images was greater in patients with erythrocyte-rich thrombi than in those with fibrin-rich thrombi. All other clinical and laboratory characteristics remained the same. Patients with erythrocyte-rich thrombi had a smaller number of recanalization maneuvers, shorter procedure times, a shorter time interval between arrival and recanalization, and a higher percentage of stent retrievers in the final recanalization procedure. The occluded vessels did not differ significantly. Conclusions: In this study, erythrocyte-rich thrombus was associated with noncardioembolic etiology, higher thrombus density, and reduced procedure time.

The purpose of this study was to investigate postural stability and lower leg muscular activity in male collegiate soccer players with functional ankle instability (FAI), during a diagonal landing. Twenty-two male collegiate soccer players were divided into an FAI group (n = 11) and healthy control group (n = 11). Muscle reaction times for sudden ankle inversion were measured to evaluate neuromuscular control in the peroneus longus (PL), peroneus brevis (PB), tibialis anterior (TA), gastrocnemius lateral head (GL), and gastrocnemius medial head (GM). Time to anteroposterior stabilization (TTSAP), time to mediolateral stabilization (TTSML), and activity of these muscles during a diagonal single-leg landing was measured. Reaction times in the peroneus muscles were delayed in the FAI group, compared to the control group (PL: P < 0.01, PB: P = 0.02). TTSML was increased in the FAI group, compared to the control group (P = 0.02). Muscular activity of PL, PB, and TA were reduced in the FAI group, compared to controls, during a diagonal single-leg landing (PL: P < 0.05, from 87 ms pre-initial contact [pre-IC] to 108 ms post-initial contact [post-IC], PB: P < 0.05, from 180 ms pre-IC to 123 ms post-IC, TA: P < 0.05, from 65 ms to 203 ms post-IC). Male collegiate soccer players with FAI had increased TTSML and reduced muscle activity in PL, PB, and TA during diagonal single-leg landing. It is important for clinicians to assess the postural stability and function of the lower leg muscle activity, during rehabilitation after ankle sprains.

The dispersal mode of estuarine invertebrates has a strong effect on genetic variability and phenotypic expression, potentially maintaining gene flow among widely separated populations or limiting connectivity among close ones. Understanding the dispersal strategies effects can support adequate strategies for environment management and understand the evolutionary history of the studied species. A comparative study on the effect of larval dispersal strategies (export vs retention) along the overall geographic distribution ranges of adult populations of two co‐distributed fiddler crab species was performed. Geometric morphometric techniques were used to evaluate morphological differentiation in the shape of the carapace and major cheliped propodus in 10 populations of Minuca mordax and five populations of Leptuca leptodactyla. Potential genetic differentiation was assessed using DNA sequence data from up to 170 fiddler crab specimens, corresponding to the mitochondrial gene cytochrome c oxidase subunit 1 (COX1). Patterns of genetic and morphological characteristics diverged among populations of both species. In terms of morphology, populations of both species showed intraspecific variation in the shape of the carapace and, to a lesser extent, in the major cheliped propodus. This observed intraspecific variation followed a clear geographic pattern of morphometric differentiation, in which the geographic origin is associated with a phenotypic response to the environmental diversity along the extended Brazilian coast. In contrast, there are shared haplotypes in populations separated by more than 4000 km, but with significant ΦST values among most populations of L. leptodactyla and M. mordax, suggesting a moderate to high level of gene flow. Therefore, it can be concluded that the split of the Central South Equatorial Current has not acted as an efficient long‐term barrier to the dispersal of larvae in both species. In M. mordax, a slight limitation of genetic exchange can be observed between the southernmost populations and the remaining ones. This first evidence of genetic structuring within this widely distributed species is consistent with its documented strategy to retain larvae in the estuarine environments. However, occasional transport of larvae to more open coastal waters seems to maintain stepwise gene flow between neighboring populations. Overall, our results still provide evidence of more pronounced genetic homogeneity in a species with a larval export strategy (L. leptodactyla) compared to a species with a larval retention strategy (M. mordax). This suggests that larval dispersal strategies, coupled with the microhabitat in which the respective species occur, have a noticeable effect on the degree of gene flow. Most likely, these biological aspects are further influenced by the estuarine and coastline geomorphology. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this study was to describe the behavior of newly-hatched juveniles and maternal care in Aegla schmitti. The experiment was conducted using seven ovigerous females with eggs at different stages of embryonic development and 12 eggs that had been placed in a separate aquarium. We observed asynchronous hatching in all females, with a mean of 66 hatched juveniles per female. The females also exhibited extended maternal care, allowing the juveniles to remain inside their abdominal chamber or on other parts of their body in the first few days after hatching. The juveniles that hatched in a separate aquarium fed on the remaining eggs, despite food being available. The incubation period and number of hatched eggs are highly variable between species with direct development, with no clear pattern being evident. However, asynchrony in hatching time is apparently common among freshwater anomurans, most likely due to the environmental conditions in which they live. Parental care is an important trait for crustaceans that live in osmotically unfavorable environments, such as freshwater, increasing the survival rate of juveniles.

ABSTRACT A study on relative growth, sexual dimorphism and ontogenetic trajectory was carried out in a population of the aeglidAegla marginata coming from Barrinha River, Iguape River Basin, Tunas do Paraná, Paraná State, Brazil. The size the of morphological sexual maturity was estimated for males and females. The analysis of sexual dimorphism and ontogenetic trajectory were performed using geometric morphometric technique. Males reach maturity with 10.58 mm of carapace length (CL) and females with 10.38 mm CL. Sexual size dimorphism was only visible among adults, with males reaching larger sizes. This is probably related to the reproductive strategy of males. However, sexual shape dimorphism was found for both juveniles and adults: the posterior region of the carapace was wider in females. As the contrast of this feature was stronger in adults, it can be considered that large abdomen is advantageous for egg incubation. The allometric trajectories of juveniles presented similar directions, becoming divergent during the adult phase. The shape variation inA. marginataoccurred gradually throughout its development, with no abrupt transformation upon reaching sexual maturity. The reproductive adaptation is the main reason for the morphological variation within populations ofA. marginata.

BackgroundEndovascular therapy has been shown to be effective in patients with acute cerebral large‐vessel occlusion, but real‐world efficacies are unknown. Methods and ResultsWe conducted a prospective registry at 46 centers between October 2014 and January 2017. Eligible patients were those who were aged 20 years or older, with acute cerebral large‐vessel occlusion, and who were hospitalized within 24 hours of the onset. We enrolled both consecutive patients who were treated with or without endovascular therapy. Endovascular therapy included thrombectomy, balloon angioplasty, stenting, local fibrinolysis, and piercing. The primary outcome was a favorable outcome as defined by a modified Rankin Scale of 0 to 2 at 90 days after onset. Secondary outcomes were modified Rankin Scale of 0 to 1 and mortality. Safety outcomes were intracerebral hemorrhage or a recurrence of ischemic stroke. We constructed the 2242 (1121 each) propensity score–matched patients cohort based on a propensity score for endovascular therapy and estimated the adjusted odds ratio, followed by sensitivity analyses on original 2399 (1278 in endovascular therapy versus 1121 in no endovascular therapy) patients. In the propensity score–matched cohort, favorable outcomes were observed in 35.3% and 30.7% of patients in the endovascular therapy and no endovascular therapy groups, respectively (P=0.02). The adjusted odds ratio for the favorable outcome was 1.44 (95% confidence interval, 1.10–1.86, P=0.007). The efficacy of endovascular therapy in achieving favorable outcomes did not differ between our subgroups and in the sensitivity analyses. ConclusionsEndovascular therapy decreased disabilities at 90 days in real‐world patients with acute cerebral large‐vessel occlusion. Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT02419794.

Medial tibial stress syndrome (MTSS) is one of the most common causes of exercise-induced lower leg pain in running athletes. The purpose of this study was to compare plantar flexor activation changes in response to different strike patterns during barefoot and shod running in subjects with and without MTSS. The changes were assessed by observing motion characteristics derived from mechanical factors. The 15 collegiate soccer players who volunteered to participate were divided into two groups (7 MTSS, 8 non-MTSS). Three-dimensional marker positions were recorded with a 12-camera motion capture system (Vicon) operating at 250 Hz while the subjects ran along a runway at 3.3 m/s. Each subject completed the running with and without shoes, and different strike patterns as the forefoot strike pattern (FFS) and rearfoot strike pattern (RFS) were collected. Plantar flexor activation was investigated by software for interactive musculoskeletal modeling (SIMM) based on how the activation ratio changed from 0 to 1 at landing. Compared to controls, the MTSS group had higher tendency muscle activity of the plantar flexors that involved the peroneal muscle during first half of stance (p

The standard CHOP therapy for peripheral T-cell lymphoma has resulted in unsatisfactory outcomes and it is still not clear what is the optimal front-line therapy. We conducted a multicenter phase II study of dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone (EPOCH) for untreated peripheral T-cell lymphoma patients. In this prospective study, 41 patients were treated with dose-adjusted-EPOCH as initial therapy: peripheral T-cell lymphoma-not otherwise specified, n=21; angioimmunoblastic T-cell lymphoma, n=17; anaplastic lymphoma kinase-positive anaplastic large cell lymphoma, n=2; and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma, n=1. Median patient age was 64 years (range: 32–79 years). According to the International Prognostic Index criteria, 51.2% were at high-intermediate or high risk. The overall response and complete response rates were 78.0% [95% confidence interval (CI): 62.4–89.4%] and 61.0% (95%CI: 44.5–75.8%), respectively. At the median follow up of 24.0 months, the 2-year progression-free survival and overall survival were 53.3% (95%CI: 36.4–67.5%) and 73.2% (95%CI: 56.8–84.1%), respectively. The younger patients (≤ 60 years old) had a high response rate (overall response 94.1% and complete response 70.6%) and survival rate (progression-free survival 62.5% and overall survival 82.4%). The most common grade ≥ 3 adverse events were neutropenia (74.5%), anemia (40.8%), thrombocytopenia (22.0%), and febrile neutropenia (9.0%). Dose-adjusted-EPOCH had a high response rate with a tolerable toxicity profile. Our results indicate that dose-adjusted-EPOCH is a reasonable first-line approach for peripheral T-cell lymphoma patients and may improve outcomes.

Ankle inversion sprains are the most common football-related injuries. About 74% of patients with residual symptoms such as general ankle instability, the ankle suddenly giving way, or recurrent ankle sprains, may develop chronic ankle instability. Balance training is a common rehabilitation procedure used after an ankle sprain. However, the influence of balance training on the muscle reaction time and muscle chain reaction is still unclear. Accordingly, this study examines how balance training influences muscle reaction time and muscle chain reaction. This controlled laboratory study involved 33 male college football players assessed for existence/non-existence of ankle functional instability (FI). The subjects were then divided into a group of 12 players with FI who underwent balance training (FI group), 12 players without FI who underwent balance training (Con group), and 9 players without FI who did not undergo balance training (NTr group). Muscle reaction times during ankle varus simulation with Trap-door were measured. The main effect was seen between the peroneus muscle group and anterior tibialis muscle in the Con and NTr groups. In the FI group, no significant main effect on the muscle was seen, but the main effect on intervention period was significant. Balance training reduced the muscle reaction time of the FI group. Results suggest that balance training may improve muscle reaction time. However, the absence of a significant difference between the peroneus muscle group and anterior tibialis muscle in the FI group after balance training indicates that the muscle chain reaction did not recover to the level of an uninjured leg.