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Takashi Kojima,1,2 Akeno Tamaoki,2 Kazuo Ichikawa,3 Yuya Satoh,4 Ryota Tomemori,5 Keizo Watanabe,6 Asato Hasegawa,2 Ayako Sawaki,2 Tatsushi Kaga2 1Department of Ophthalmology, Nagoya Eye Clinic, Nagoya, Aichi, Japan; 2Department of Ophthalmology, Japanese Community Healthcare Organization Chukyo Hospital, Nagoya, Aichi, Japan; 3Department of Ophthalmology, Chukyo Eye Clinic, Nagoya, Aichi, Japan; 4Department of Ophthalmology, Satoh Yuya Eye Clinic, Sendai, Miyagi, Japan; 5Department of Ophthalmology, Tomemori Eye Clinic, Hashimoto, Wakayama, Japan; 6Department of Ophthalmology, Minami Osaka Eye Clinic, Sennangun, Osaka, JapanCorrespondence: Takashi Kojima, Email tkojkoj@mac.comPurpose: We evaluated the effect of optimization of the intraocular lens (IOL) power calculation formula SRK/T and Barrett Universal II (BU II) in long eyes (≥ 26 mm: group L) and short eyes (≤ 22 mm: group S) using axial length calculated from segmented refractive indices (SRI).Setting: Multicenter study at five sites in Japan.Design: Retrospective observational study.Methods: This study included 461 eyes of 461 patients (mean age 73.8 ± 8.4 years) who underwent cataract surgery. The predicted refractive error (PRE) was compared between the SRI (ARGOS) and the equivalent refractive index (ERI) biometers (IOLMasterTM 700). The patients were randomly divided into two groups, a learning group and a validation group. The optimization constants were determined in the learning group, and the optimization constants were subsequently applied to the validation group and compared with the ERI biometer results.Results: Using both SRK/T and BU II, the validation group’s PRE using optimization constants for the SRI biometer in group L was significantly smaller than that using the ERI biometer (p< 0.001, p< 0.01). In group L, the arithmetic PRE of Barrett UII formula with SRI showed a significant improvement after optimization compared to before optimization (p< 0.0001). In group S, the arithmetic PRE of SRK/T and Barrett UII formula with SRI showed a significant improvement (p< 0.0001, p< 0.0001).Conclusion: In long and short eyes, the current study revealed that optimization of the SRK/T and Barrett formula constants for the SRI biometer was beneficial to achieve accurate refractive outcomes after cataract surgery.Keywords: segmented refractive index, intraocular lens power calculation, Sanders-Retzlaff-Kraff theoretic, Barrett universal II, optimization

Although the potential of traditional domestic rainwater harvesting systems (RWHSs) is easily determined, objective knowledge is required to determine their sustainability or scientific validity. We aimed to broadly review recent trends and emerging opportunities for research on the potential of RWHSs in the global context. We reviewed three types of representative RWHSs: water cellars, stepwells, and qanats. In total, 16 potential categories were defined. First, to date, 50% of the categories of potential have been demonstrated but are not considered beneficial, have been proven only in limited locations, only in limited sampling sets, or are theoretical. Second, whether the involvement of other disciplines has resulted in an expansion of the research scope or whether a particular potential has not been comprehensively explained remains to be determined by researchers. Third, potential that has emerged in the 21st century is not beyond our imagination such as tourism potential and ecological potential. Therefore, researchers should actively explore and incorporate new innovative technologies with RWHSs to explore new potential. The findings of this study offer a viable research framework for investigating the evolution of the discipline and contribute to the development of critical thinking in the analysis of the potential of RWHSs.

The designation of historic conservation areas (DHCAs) from the cities classified as “National Famous Historical and Cultural City” (NFHC-city) is the key tool for maintaining large-scale historic environments, wherein the boundaries are blurred because of redevelopment. Therefore, exploring potential historic conservation area is fundamentally important. In this study, we examined historic urban areas in 11 old colonial cities (concessions and leased territories) to determine the potential historic conservation areas (P-HCAs). Our results suggest that P-HCAs are characterized by relatively small size, minimal residential use, and irregular morphological boundaries, except in some non-NFHC-cities, where P-HCAs are located adjacent to officially protected public and commercial buildings. The DHCA boundaries and extent of urban development influence the storage of P-HCA. The approach and method proposed in this study not only provide reference for the conservation and replenishment of the historic districts in China, but are also applicable for other countries.

Purpose: The optimal treatment following endocrine therapy (ET) plus a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) has not been established. We aimed to investigate treatment patterns and time to treatment failure (TTF) of subsequent therapy after palbociclib in a Japanese real-world setting. Methds: This retrospective observational study used de-identified data of patients with advanced breast cancer treated with palbociclib, using a nationwide claims database (April 2008 to June 2021). Measures included the type of subsequent therapies after palbociclib (endocrine-based therapy: ET alone, ET + CDK4/6i, and ET + mammalian target of rapamycin inhibitor [mTORi]; chemotherapy; chemotherapy + ET; and others) and their TTFs. The median TTF and 95% confidence interval (CI) were estimated using the Kaplan-Meier method. Results: Of 1170 patients treated with palbociclib, 224 and 235 received subsequent therapies after first- and second-line palbociclib treatment, respectively. Among them, 60.7% and 52.8% were treated with endocrine-based therapies as first subsequent therapy, including ET + CDK4/6i (31.2% and 29.8%, respectively). The median TTF (95% CI) of ET alone, ET + CDK4/6i, and ET + mTORi as first subsequent therapy after first-line palbociclib were 4.4 (2.8–13.7), 10.9 (6.5–15.6), and 6.1 (5.1–7.2) months, respectively. No apparent relationship between the treatment duration of prior ET + palbociclib and subsequent abemaciclib was observed. Conclusion: This real-world study revealed that one-third of the patients received sequential CDK4/6i after ET + palbociclib, and treatment duration of ET + CDK4/6i following ET + palbociclib was the longest among the treatment options. Further data are awaited to determine whether ET + targeted therapy with CDK4/6i and mTORi provides acceptable treatment options following ET + palbociclib.

Abstract Background With advances in breast cancer treatment, the importance of de-escalation therapy to reduce harm during the treatment of elderly patients has attracted attention in recent years. Certain patient populations are expected to have a superior response to anti-HER2 drugs, particularly those with human epidermal growth factor receptor type 2 (HER2)-positive breast cancer. In this report, we describe our experience of dramatic anti-HER2 drug response in a patient who achieved pathological complete response (pCR) with a single dose of trastuzumab. Case presentation An 88-year-old woman presented with a 2-cm palpable mass in the left breast. Vacuum-assisted breast biopsy, ultrasonography, and positron emission tomography–computed tomography revealed estrogen receptor-negative and HER2-positive, T1N0M0, stage I breast cancer. Mastectomy was scheduled within 2 months of the initial visit; however, the patient was anxious about the length of the waiting period and requested medication in the interim. Therefore, prior to surgery, one cycle of trastuzumab monotherapy was administered at the discretion of the attending physician. Postoperative pathology showed no remnant of invasive carcinoma and pCR with only a 0.2-mm ductal carcinoma in situ remnant. The patient refused further medication after surgery because of severe diarrhea after trastuzumab administration. Postoperative treatment was limited to follow-up, and no recurrence was observed at 1 year and 6 months postoperatively. Conclusion This case suggests that trastuzumab monotherapy may be effective in certain patients with HER2-positive breast cancer. In the future, identifying patients who are more likely to respond to trastuzumab, as in this case, will allow for more options regarding de-escalation therapy without chemotherapy, particularly in elderly patients who are concerned about the side effects of chemotherapy.

ABSTRACT Aims/Introduction The discrepancy between HbA1c and glucose exposure may have significant clinical implications; however, the association between the hemoglobin glycation index (HGI) and clinical parameters in type 1 diabetes remains controversial. This study aimed to find the factors associated with HGI (laboratory HbA1c − predicted HbA1c derived from the continuous glucose monitoring [CGM]). Materials and Methods We conducted a cross‐sectional study of adults with type 1 diabetes (n = 211, age 50.9 ± 15.2 years old, female sex = 59.2%, duration of CGM use = 2.1 ± 1.0 years). All subjects wore the CGM for 90 days before HbA1c measurement. Data derived from the FreeStyle Libre sensor were used to calculate the glucose management indicator (GMI) and glycemic variability (GV) parameters. HGI was defined as the difference between the GMI and the laboratory HbA1c levels. The participants were divided into three groups according to the HGI tertile (low, moderate, and high). Multivariate regression analyses were performed. Results The female sex ratio, HbA1c, and % coefficient of variation (%CV) significantly increased over the HGI tertile, while eGFR and Hb decreased over the HGI tertile. In multivariate analysis, the factors associated with HGI were %CV and eGFR, after adjusting for HbA1c level and sex (R2 = 0.44). Conclusions This study demonstrated that HGI is associated with female sex, eGFR, and some glycemic variability indices, independently of HbA1c. Minimizing glycemic fluctuations might reduce HGI. This information provides diabetic health professionals and patients with personalized diabetes management for adults with type 1 diabetes.

Abstract Background The aim of this study was to determine a predictive indicator of gemcitabine (GEM) efficacy in unresectable pancreatic cancer using tissue obtained by endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNA). Methods mRNAs extracted from 35 pancreatic tubular adenocarcinoma tissues obtained by EUS-FNA before GEM-treatment were studied. mRNAs were amplified and applied to a Focused DNA Array, which was restricted to well-known genes, including GEM sensitivity-related genes, deoxycytidine kinase (dCK), human equilibrative nucleoside transporter 1 (hENT1), hENT2, dCMP deaminase, cytidine deaminase, 5'-nucleotidase, ribonucleotide reductase 1 (RRM1) and RRM2. mRNA levels were classified into high and low expression based on a cut-off value defined as the average expression of 35 samples. These 35 patients were divided into the following two groups. Patients with partial response and those with stable disease whose tumor markers decreased by 50% or more were classified as the effective group. The rest of patients were classified as the non-effective group. The relationship between GEM efficacy and mRNA expression was then examined by chi-squared test. Results Among these GEM sensitivity-related genes, dCK alone showed a significant correlation with GEM efficacy. Eight of 12 patients in the effective group had high dCK expression, whereas 16 of 23 patients in non-effective group had low dCK expressions (P = 0.0398). Conclusion dCK mRNA expression is a candidate indicator for GEM efficacy in unresectable pancreatic cancer. Quantitative mRNA measurements of dCK using EUS-FNA samples are necessary for definitive conclusions.

The purpose of the present study is to examine whether performance on the "TOEFL iBT"® Reading practice test is affected by 3 different levels of feedback provided to learners upon completion of reading exercises: (a) correctness of learner response (the knowledge of correct results [KCR] feedback), (b) KCR feedback and rationales for correct/incorrect answers, and (c) KCR feedback and the rationales along with on-demand video lectures. Japanese learners of English completed 18 reading exercises and reviewed the results by using the type of feedback provided to the group to which each learner had been assigned. They also completed 2 TOEFL iBT Reading test forms: 1 as a pretest and 1 as a posttest. A multilevel modeling analysis of data from 193 participants who completed the study showed that despite a gain of over 3 scaled score points on the TOEFL iBT Reading test from the pretest to the posttest, the level of feedback was not found to affect the test score. A learner background variable, previous knowledge about the TOEFL iBT test, was identified as a predictor positively related to the test score. Moreover, a series of ANOVAs conducted on learner survey data suggested that the level of feedback affected the degree to which study participants perceived the usefulness of the study materials in understanding different item types that appear on the TOEFL iBT Reading section and in developing strategies for understanding the gist of the text within a short time.

Abstract Background Stroke remains a major public health concern in the United States and a leading cause of long-term disability in adults. Dynamic body weight support (DBWS) systems are popular technology available for use in clinical settings such inpatient rehabilitation. However, there remains limited studies in such inpatient settings that compare DBWS to standard of care (SOC) using real world outcome measures. For survivors of acute ischemic stroke, we determine if incorporating a dynamic body weight support (DBWS) system into inpatient therapy offers greater improvement than standard of care (SOC). Methods A retrospective chart review included 52 individuals with an acute ischemic stroke admitted to an inpatient rehabilitation facility. Functional Independence Measure (FIM) data, specifically changes in FIM at discharge, served as the primary outcome measure. Patient cohorts received either therapies per SOC or therapies incorporating DBWS. Regardless of cohort group, all patients underwent therapies for 3 h per day for 5 days a week. Results For both groups, a statistically and clinically significant increase in total FIM (P

Purpose: To gauge the effects of treatment practices on prognosis for older patients with HER2-positive early breast cancer, particularly to determine whether adjuvant trastuzumab alone can offer benefit over no adjuvant therapy. This is a prospective cohort study which accompanies the RESPECT that is a randomized-controlled trial (RCT). Methods: Patients who declined the RCT were treated based on the physician's discretion. We studied the 1) trastuzumab-plus-chemotherapy group, 2) trastuzumab-monotherapy group, and 3) non-trastuzumab group (no therapy or anticancer therapy without trastuzumab). The primary endpoint was disease-free survival (DFS), which was compared using the propensity-score method. Relapse-free survival (RFS) and health-related quality of life (HRQoL) were assessed. Results: We enrolled 123 patients aged over 70 years (median: 74.5). Treatment categories were: trastuzumab-plus-chemotherapy group (n = 36, 30%), trastuzumab-monotherapy group (n = 52, 43%), and non-trastuzumab group (n = 32, 27%). The 3-year DFS was 96.7% in trastuzumab-plus-chemotherapy group, 89.2% in trastuzumab-monotherapy group, and 82.5% in non-trastuzumab group. DFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted hazard ratio; HR: 3.29; 95% CI: 1.15–9.39; P = 0.026). The RFS in non-trastuzumab group was lower than in trastuzumab-plus-chemotherapy and trastuzumab-monotherapy groups (propensity-adjusted HR = 7.80; 95% CI: 2.32–26.2, P

Adipose tissue macrophages (ATMs) play an important role in obesity and inflammation, and they accumulate in adipose tissue (AT) with aging. Furthermore, increased ATM senescence has been shown in obesity-related AT remodeling and dysfunction. However, ATM senescence and its role are unclear in age-related AT dysfunction. Here, we show that ATMs (a) acquire a senescence-like phenotype during chronological aging; (b) display a global decline of basic macrophage functions such as efferocytosis, an essential process to preserve AT homeostasis by clearing dysfunctional or apoptotic cells; and (c) promote AT remodeling and dysfunction. Importantly, we uncover a major role for the age-associated accumulation of osteopontin (OPN) in these processes in visceral AT. Consistently, loss or pharmacologic inhibition of OPN and bone marrow transplantation of OPN–/– mice attenuate the ATM senescence-like phenotype, preserve efferocytosis, and finally restore healthy AT homeostasis in the context of aging. Collectively, our findings implicate pharmacologic OPN inhibition as a viable treatment modality to counter ATM senescence-mediated AT remodeling and dysfunction during aging.

BackgroundClinical guidelines recommend regular serum lithium monitoring every 3 to 6 months. However, in the real world, only a minority of patients receive adequate monitoring. ObjectiveThis study aims to examine whether the use of the electronic health record (EHR)–nested reminder system for serum lithium monitoring can help achieve serum lithium concentrations within the therapeutic range for patients on lithium maintenance therapy. MethodsWe conducted an unblinded, single-center, EHR-nested, parallel-group, superiority randomized controlled trial comparing EHR-nested reminders with usual care in adult patients receiving lithium maintenance therapy for mood disorders. The primary outcome was the achievement of therapeutically appropriate serum lithium levels between 0.4 and 1.0 mEq/L at 18 months after enrollment. The key secondary outcomes are included as follows: the number of serum lithium level monitoring except for the first and final monitoring; exacerbation of the mood disorder during the study period, defined by hospitalization, increase in lithium dose, addition of antipsychotic drugs or mood stabilizers, or addition or increase of antidepressants; adherence defined by the proportion of days covered by lithium carbonate prescription during the study period. ResultsA total of 111 patients were enrolled in this study. A total of 56 patients were assigned to the reminder group, and 55 patients were assigned to the usual care group. At the follow-up, 38 (69.1%) patients in the reminder group and 33 (60.0%) patients in the usual care group achieved the primary outcome (odds ratio 2.14, 95% CI 0.82-5.58, P=.12). The median number of serum lithium monitoring was 2 in the reminder group and 0 in the usual care group (rate ratio 3.62; 95% CI 2.47-5.29, P

In this study, we use the integrated concept of the “historical water supply facility” to advance the regional characterization of point-like facilities. Eighteen villages in eastern Shanxi Province, which has a typical semi-arid climate, were taken as the study area, and data were collected by field observations and in-depth interviews. The results reveal that the natural environment, specifically the terrain and river systems, influenced the formation of water cellars and water-logging pools, but had less direct effects on well construction. The formation of these facilities was eventually influenced by the residents pursuing stability and exhibiting a preference for water resources. Furthermore, under the pressure of survival, the types of facilities gradually diversified, while the numbers changed dynamically. Additionally, water cellars exhibited a minor correlation with the flood prevention, environmental sanitation, and yard drainage facilities of the village. These findings demonstrate that the core issue in the formation of diversified regional water supply characteristics is the attempt to find a balance between nature and water use/flood prevention, an embodiment of the explicit recognition of limited self-ability.

Several genetic defects, including a mutation in myosin heavy chain 11 (Myh11), are reported to cause familial thoracic aortic aneurysm and dissection (FTAAD). We recently showed that mice lacking K1256 of Myh11 developed aortic dissection when stimulated with angiotensin II, despite the absence of major pathological phenotypic abnormalities prior to stimulation. In this study, we used a comprehensive, data-driven, unbiased, multi-omics approach to find underlying changes in transcription and metabolism that predispose the aorta to dissection in mice harboring the Myh11 K1256del mutation. Pathway analysis of transcriptomes showed that genes involved in membrane transport were downregulated in homozygous mutant (Myh11ΔK/ΔK) aortas. Furthermore, expanding the analysis with metabolomics showed that two mechanisms that raise the cytosolic Ca2+ concentration—multiple calcium channel expression and ADP–ribose synthesis—were attenuated in Myh11ΔK/ΔK aortas. We suggest that the impairment of the Ca2+ influx attenuates aortic contraction and that suboptimal contraction predisposes the aorta to dissection.

Abstract Mechanical stimulation such as flood flow often plays a vital role in the growth and maintenance of a living body, and it is important to investigate cell responses to mechanical stimulation. To date, cell responses to mechanical stimulation have been investigated in detail. However, the cell responses have been little known in a cell sheet. In the present study, a small cyclic strain (CS) of ~0.5% generated by a nanoporous gold actuator was loaded on a cell sheet of fibroblasts, and the effects of the CS on cell orientation were investigated. Individual cells were randomly distributed after the CS application, whereas cells were oriented in a specific direction after the CS application for the cell sheet. Thus, the CS had a different effect on the cell sheet from that on the individual cells. It is suggested that the cadherin/p-120 catenin complex played an important role in the cell response to mechanical stimulation in a cell sheet.

Accumulating evidence suggests that gut microbes modulate brain plasticity via the bidirectional gut-brain axis and play a role in stroke rehabilitation. However, the microbial species alterations associated with stroke and their correlation with functional outcome measures following acute stroke remain unknown. Here we measure post-stroke gut dysbiosis and how it correlates with gut permeability and cognitive functions in 12 stroke participants, 18 controls with risk factors for stroke, and 12 controls without risk factors. Stool samples were used to measure the microbiome with whole genome shotgun sequencing and leaky gut markers. We genotyped APOE status and measured diet composition and motor, cognitive, and emotional status using NIH Toolbox. We used linear regression methods to identify gut microbial associations with cognitive and emotional assessments. We did not find significance differences between the two control groups. In contrast, the bacteria populations of the Stroke group were statistically dissimilar from the control groups. Relative abundance analysis revealed notable decreases in butyrate-producing microbial taxa, secondary bile acid-producing taxa, and equol-producing taxa. The Stroke group had higher levels of the leaky gut marker alpha-1-antitrypsin in the stool than either of the groups and several taxa including Roseburia species (a butyrate producer) were negatively correlated with alpha-1-antitrypsin. Stroke participants scored lower on memory testing than those in the two control groups. Stroke participants with more Roseburia performed better on the picture vocabulary task; more Bacteroides uniformis (a butyrate producer) and less Escherichia coli (a pro-inflammatory species) reported higher levels of self-efficacy. Intakes of fiber, fruit and vegetable were lower, but sweetened beverages were higher, in the Stroke group compared with controls. Vegetable consumption was correlated with many bacterial changes among the participants, but only the species Clostridium bolteae, a pro-inflammatory species, was significantly associated with stroke. Our findings indicate that stroke is associated with a higher abundance of proinflammatory species and a lower abundance of butyrate producers and secondary bile acid producers. These altered microbial communities are associated with poorer functional performances. Future studies targeting the gut microbiome should be developed to elucidate whether its manipulation could optimize rehabilitation and boost recovery.

There are many options for treating human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC), and the best sequential or salvage treatment is still debated. This report outlines a case of a 59-year-old woman with HER2-positive MBC. She received HER2 triple blockade treatment using lapatinib, trastuzumab, and pertuzumab. Before triple blockade treatment, she had already received a total of 10 anti-HER2 therapy regimens in 14 years. Worsening lymphangitic carcinomatosis was determined by computed tomography (CT) in January 2020, as evidenced by dyspnea on exertion, and combination treatment with lapatinib, trastuzumab, and pertuzumab was initiated. After five cycles of combination treatment, CT and chest radiography demonstrated significant improvement in lymphangitic carcinomatosis. The dose of lapatinib was reduced at the third cycle and discontinued because of an adverse event of grade 3 diarrhea. In this case, HER2 triple blockade showed a dramatic response for treating lymphangitic carcinomatosis in a patient with heavily treated HER2-positive MBC.

Abstract Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of paclitaxel (PTX). There is no known prophylactic measure, although there are some reports of prevention with compression therapy using surgical gloves. On account of its predominantly subjective symptoms, it is difficult to exclude bias when assessing for CIPN. In this study, we assessed the effectiveness of the same procedure for the prevention of paclitaxel-induced PN based on a double-blind study design. Methods The patients with early and recurrent breast cancer (with no prior PTX exposure) initiating weekly chemotherapy with PTX 80 mg/m2 were enrolled. Each patient donned two gloves on each hand at every PTX infusion. Two one-size-smaller gloves were donned on one hand (study side) and two normal-size gloves were donned on the other hand (control side) during 90 min from 30 min before the infusion to 30 min after the end of the infusion. Study side are blind for both patients and assessing physicians according to determination of the study side by research nurses in the chemotherapy unit. The primary outcome was the difference in the frequency of CIPN (motor/sensory) determined by the physician using the common terminology criteria for adverse events (CTCAE v4.0), with an evaluation at each cycle of PTX infusion. McNemar test was used to assess the primary outcome. Results Between July 2017 and November 2018, 56 patients were enrolled and 49 patients were evaluated. Overall, Grade ≥ 2 PN (sensory) was observed in 30.6 and 36.7% in the study and control sides, respectively (McNemar p = 0.25). PN (motor) was observed in 4.1 and 6.1% in the study and control sides, respectively (McNemar p = 1.0). Conclusion Surgical glove compression therapy showed no statistically significant effect on the incidence of PTX-induced PN. Trial registrations This study was registered with the University Hospital Medical Information Network (UMIN) Clinical Trials Registry managed by the National University Hospital Council of Japan ( UMIN000027944 ). Registered 26 June 2017.

Reciprocality, also known as reciprocal situation or reciprocal constructions, constitutes an expression which describes both the forms and meaning of an activity embodying a mutual relation. Papuan Malay, a pidginized lingua franca in Western New Guinea, has three types of constructions expressing reciprocality: lexical reciprocals, prototypical syntactic reciprocals with the baku construction, and syntactic reciprocals with the discontinuous satu...satu construction. Some additional constructions are considered to be reciprocal-like. These reciprocal constructions vary in their argument structure and valence operations. In argument structure, most constructions allow two kinds of argument structure: Type 1, which takes only a subject argument, and Type 2, which takes both a subject and object, and follows the basic SVO word order. However, the object in the Type 2 construction becomes oblique-like, indicating reduced transitivity in order to accommodate the concept of mutual relation. In valence operations, reciprocals can undergo both valence decreasing and valence increasing operations. In addition, some reciprocal constructions require subject and object to be syntactically retained, even though semantically they represent the same agent-patient/goal mutual relation.

This study investigates the value of reporting the reading, listening, speaking, and writing section scores for the "TOEFL iBT"® test, focusing on 4 related aspects of the psychometric quality of the TOEFL iBT section scores: reliability of the section scores, dimensionality of the test, presence of distinct score profiles, and the section scores' generalizability for norm-referenced decisions as well as the dependability of criterion-referenced decisions for international student admission. Four operational TOEFL iBT test forms were analyzed for all examinees as well as for 3 native language (L1) groups (Arabic, Korean, and Spanish). Haberman's (2008) subscore analysis suggested that the speaking section score had added value due to its relative distinctness from the other modalities. Consistent with the subscore analysis results, a series of exploratory factor analyses (EFAs) indicated the possibility of the presence of 2 correlated factors--a reading/listening/writing factor and a speaking factor. In contrast, the CFAs conducted separately for the 3 L1 groups as well as a multiple-group confirmatory factor analyses (CFAs) identified a correlated 4-factor model with reading, listening, speaking, and writing factors as the best representation of the structure of the entire test for all examinees as well as for the 3 L1 groups. Reliability of the observed section scores for norm-referenced score interpretations and the dependability of classification decisions made based on different cut scores were generally satisfactory while they were also found to be relatively low in some circumstances. Based on the mixed results concerning the value-added information the TOEFL iBT section scores provide, recommendations for future research directions and some key issues of consideration for high-stakes decision making based on the section scores were summarized.

Background: There have been no reports of treatment effect persistence after long-term sublingual immunotherapy (SLIT) in patients with Japanese cedar (JC) pollinosis. Therefore, we conducted a post-marketing clinical trial to investigate the efficacy, safety, and effect persistence of JC pollen SLIT drops after approximately 3 years of treatment. Methods: This was an open-label trial of 233 patients with JC pollinosis who were treated with JC pollen SLIT drops for approximately 3 years (2015–2017) and followed-up for an additional 2 years (2018–2019). Efficacy and effect persistence were evaluated using nasal and ocular symptom scores, daily use of rescue medication, and Japanese Rhinoconjunctivitis Quality of Life Questionnaire scores recorded during the JC pollen dispersal season of each year. Safety was evaluated by monitoring adverse events and adverse drug reactions. Results: The mean combined total nasal symptom and medication score (range 0–18) during the peak symptom periods of 2015 through 2019 were 5.47 ± 3.38, 4.52 ± 3.13, 3.58 ± 2.63, 5.28 ± 4.01, and 6.83 ± 4.65, respectively. The percentage of patients who used no rescue medications during the same periods was 64.8%, 75.2%, 80.3%, 63.7%, and 50.3%, respectively. A total of 138 adverse drug reaction incidents were recorded in 73 of the 233 patients (31.3%), of which 134 incidents (97.1%) were mild in severity. Conclusions: JC pollen SLIT drops demonstrated treatment duration-dependent efficacy with effects that persisted for 2 years after cessation of treatment. The drug had a favorable safety profile over the 5-year study period.

Patients with peritoneal metastasis of gastric cancer have dismal prognosis, mainly because of inefficient systemic delivery of drugs to peritoneal tumors. We aimed to develop an intraperitoneal treatment strategy using amido-bridged nucleic acid (AmNA)-modified antisense oligonucleotides (ASOs) targeting synaptotagmin XIII (SYT13) and to identify the function of SYT13 in gastric cancer cells. We screened 71 candidate oligonucleotide sequences according to SYT13-knockdown efficacy, in vitro activity, and off-target effects. We evaluated the effects of SYT13 knockdown on cellular functions and signaling pathways, as well as the effects of intraperitoneal administration to mice of AmNA-modified anti-SYT13 ASOs. We selected the ASOs (designated hSYT13-4378 and hSYT13-4733) with the highest knockdown efficiencies and lowest off-target effects and determined their abilities to inhibit cellular functions associated with the metastatic potential of gastric cancer cells. We found that SYT13 interfered with focal adhesion kinase (FAK)-mediated intracellular signals. Intraperitoneal administration of hSYT13-4378 and hSYT13-4733 in a mouse xenograft model of metastasis inhibited the formation of peritoneal nodules and significantly increased survival. Reversible, dose- and sequence-dependent liver damage was induced by ASO treatment without causing abnormal morphological and histological changes in the brain. Intra-abdominal administration of AmNA-modified anti-SYT13 ASOs represents a promising strategy for treating peritoneal metastasis of gastric cancer.

Abstract Background Dynamic body-weight support (DBWS) may play an important role in rehabilitation outcomes, but the potential benefit among disease-specific populations is unclear. In this study, we hypothesize that overground therapy with DBWS during inpatient rehabilitation yields greater functional improvement than standard-of-care in adults with non-traumatic spinal cord injury (NT-SCI). Methods This retrospective cohort study included individuals diagnosed with NT-SCI and undergoing inpatient rehabilitation. All participants were recruited at a freestanding inpatient rehabilitation hospital. Individuals who trained with DBWS for at least three sessions were allocated to the experimental group. Participants in the historical control group received standard-of-care (i.e., no DBWS). The primary outcome was change in the Functional Independence Measure scores (FIMgain). Results During an inpatient rehabilitation course, participants in the experimental group (n = 11), achieved a mean (SD) FIMgain of 48 (11) points. For the historical control group (n = 11), participants achieved a mean (SD) FIMgain of 36 (12) points. From admission to discharge, both groups demonstrated a statistically significant FIMgain. Between groups analysis revealed no significant difference in FIMgain (p = 0.022; 95% CI 2.0–22) after a post hoc correction for multiple comparisons. In a secondary subscore analysis, the experimental group achieved significantly higher gains in sphincter control (p = 0.011: 95% CI 0.83–5.72) with a large effect size (Cohen’s d 1.19). Locomotion subscores were not significantly different (p = 0.026; 95% CI 0.37–5.3) nor were the remaining subscores in self-care, mobility, cognition, and social cognition. Conclusions This is the first study to explore the impact of overground therapy with DBWS on inpatient rehabilitation outcomes for persons with NT-SCI. Overground therapy with DBWS appears to significantly improve functional gains in sphincter control compared to the standard-of-care. Gains achieved in locomotion, mobility, cognition, and social cognition did not meet significance. Findings from the present study will benefit from future large prospective and randomized studies.

Although the performance of simple cognitive tasks can be enhanced if an incentive is provided, the mechanisms enabling such motivational control are not known. This study sought to uncover how mechanisms of attention and readiness are altered by reward-associated incentive stimuli. We measured EEG/ERP activity as human adults viewed a high- or low-incentive cue, experienced a short preparation interval, and then performed a simple visual search task to gain the predicted reward. Search performance was faster with high versus low incentives, and this was accompanied by distinct incentive-related EEG/ERP patterns at each phase of the task (incentive, preparation, and search). First, and most surprisingly, attention to high but not low incentive cues was actively suppressed, as indexed by a PD component in response to the incentive display. During the subsequent preparation interval, neural oscillations in the alpha frequency range were reduced after high-incentive cues, indicating heightened visual readiness. Finally, attentional orienting to the target in the search array was deployed with relatively little effort on high-incentive trials, as indexed by a reduced N2pc component. These results reveal the chain of events by which the brain's executive control mechanisms respond to incentives by altering the operation of multiple processing systems to produce optimal performance.

Anaerobic threshold (AT) is an established parameter of aerobic fitness. The incremental sit-to-stand exercise (ISTS), using one of the activities of daily living, is used to assess physical capacity in patients who are unable to safely pedal or walk. However, the effect of an alternative ISTS protocol on AT remains unclear. The aim of this study was to compare the effect of the original ISTS protocol with an alternative shortened ISTS protocol on AT values in healthy young adults, and to assess the difference in AT values obtained during the ISTS protocols and the cycle ergometer test. Twelve healthy young adults (mean [range] age: 26.8 [22–33] years, 6 men and 6 women) performed the shortened version of the ISTS (S-ISTS), the original version of ISTS (O-ISTS), and cycle ergometer (CE) tests in a randomized order. The AT values of participants were measured during each of the three tests. No significant difference in AT values was observed among the three tests. AT obtained by individuals in the S-ISTS was significantly correlated with that obtained during the O-ISTS and CE tests with r values of 0.96 and 0.81, respectively (p < 0.05). Similar to the O-ISTS and CE test, the S-ISTS test may be used as an exercise test for the assessment of AT in a clinical setting.