Miracle-dz/UniFAR-FTUs huggingface dataset:
Early results of a phase-II study of modified short-course radiotherapy combined with capecitabine and delayed surgery for T3M0 lower rectal cancer

Strong evidence of short-course 5 5Gy radiotherapy (SRT) for rectal cancer has been published [1,2], and recently, the Stockholm III trial demonstrated the feasibility of an experimental regimen involving short-course 5 5Gy radiotherapy with delayed surgery (SRT-delay) [3]. However, these regimens might still have some limitations. First, there exist concerns regarding the toxicity of the high 5-Gy fractions, even if only five fractions are administered, resulting in a comparably low total dose of 25 Gy. Second, long-course settings combined with chemotherapy improves local control, especially in highly advanced groups; however, no evidence is available regarding the combined use of chemotherapy and the short-course regimen. Thus, we proposed a modified SRT-delay regimen, which involves two modifications from the original regimen. The first is that 5Gy of each fraction is divided into two fractions (2.5Gy/fraction 2 fractions/day) to reduce each fraction dose. The second is that capecitabine, a radiosensitizer, was administered with radiotherapy to improve the treatment response. The aim of the present phase-II study was to evaluate the efficacy, tolerability and feasibility of this modified SRT-delay with concomitant use of capecitabine for T3 lower rectal cancer. The primary endpoint was response rate (total and major regression: Grade 2 and 3), and the secondary endpoints were safety (incidence of adverse events and complications), curative resection (R0) rate, downstaging and sphincter preservation.
Characterization of the hypothalamus of Xenopus laevis during development. II. The basal regions

The expression patterns of conserved developmental regulatory transcription factors and neuronal markers were analyzed in the basal hypothalamus of Xenopus laevis throughout development by means of combined immunohistochemical and in situ hybridization techniques. The connectivity of the main subdivisions was investigated by in vitro tracing techniques with dextran amines. The basal hypothalamic region is topologically rostral to the basal diencephalon and is composed of the tuberal (rostral) and mammillary (caudal) subdivisions, according to the prosomeric model. It is dorsally bounded by the optic chiasm and the alar hypothalamus, and caudally by the diencephalic prosomere p3. The tuberal hypothalamus is defined by the expression of Nkx2.1, xShh, and Isl1, and rostral and caudal portions can be distinguished by the distinct expression of Otp rostrally and Nkx2.2 caudally. In the mammillary region the xShh/Nkx2.1 combination defined the rostral mammillary area, expressing Nkx2.1, and the caudal retromammillary area, expressing xShh. The expression of xLhx1, xDll4, and Otp in the mammillary area and Isl1 in the tuberal region highlights the boundary between the two basal hypothalamic territories. Both regions are strongly connected with subpallial regions, especially those conveying olfactory/vomeronasal information, and also possess abundant intrahypothalamic connections. They show reciprocal connections with the diencephalon (mainly the thalamus), project to the midbrain tectum, and are bidirectionally related to the rhombencephalon. These results illustrate that the basal hypothalamus of anurans shares many features of specification, regionalization, and hodology with amniotes, reinforcing the idea of a basic bauplan in the organization of this prosencephalic region in all tetrapods. J. Comp. Neurol. 522:1102–1131, 2014. © 2013 Wiley Periodicals, Inc.
Associations between the use of do-not-resuscitate orders and length of stay in patients with stroke.

OBJECTIVES The study sought to describe the association between do-not-resuscitate (DNR) orders and length of hospital stay (LOS), and how the association varies according to in-hospital mortality, timing of the DNR order, and admission severity of illness. METHODS The authors conducted a retrospective cohort analysis involving standardized review of patients' medical records. The study was performed at 30 acute care hospitals in a large metropolitan area. The authors studied the data of 13,337 consecutive patients with a primary diagnosis of stroke discharged in 1991 through 1994. RESULTS Do-not-resuscitate orders were written for 22% (n = 2,898) of the sample. In all patients, mean LOS was longer in patients with DNR orders than in patients without orders (12.0 versus 9.5 days; P < 0.001). A series of Cox regression analyses were performed to adjust LOS for admission severity of illness and other covariates. In analyses of patients discharged alive (n = 12,011), LOS was similar in patients with DNR orders written on days 1 to 2 compared with patients without DNR orders. However, LOS was longer in patients with DNR orders written on days 3 to 7 (Hazard Ratio [HR], 1.59; 95% CI, 1.43-1.77) and on day 8 or later (HR, 2.72; 95% CI, 2.34-3.16). In analyses of patients who died (n = 1,326), LOS was shorter for patients with DNR orders written on days 1 and 2 (HR, 0.59; 95% CI, 0.49-0.71) than for patients without DNR orders but was longer among patients with DNR orders written on day 8 or later (HR, 2.58; 95% CI, 2.06-3.22). In analyses stratified by admission severity, the relative effect of a DNR order tended to be less in patients with higher severity. CONCLUSIONS The relationship between DNR orders and LOS is complex and varies according to in-hospital mortality, the timing of the DNR order, and admission severity of illness. These findings highlight the importance of explicitly accounting for such factors in studies evaluating the implications of DNR orders on the costs of hospital care.
Physiology, behaviour and welfare of fish during recreational fishing and after release

Abstract This review investigates how recreational fishing affects the physiology, behaviour, and welfare of fish. Sentience and the capacity of fish to experience pain, suffering and fear are discussed, and practical recommendations for improving the treatment of fish during recreational fishing are provided. Handling procedures used in recreational fishing should match the environment where the fish is caught and the size and strength of the fish. Minimising the number of hooks on lures and baits, and using barbless hooks and circle hooks generally reduce rates of injury and the severity of tissue trauma. Capture time, handling time, and exposure to air play significant roles in the stress responses of fish and should be minimised by anglers. Keepnets, gaffs, landing-nets, live-wells and other restraining devices should only be used when necessary because each device can prolong or intensify the negative influences of catching fish by hook-and-line. The use of fish as bait is discouraged unless they have been euthanised. Euthanasia offish used as bait or fish captured recreationally should include a stunning blow to the head, followed by bleeding-out, or pithing the brain and spinal cord. Fish should be euthanised if they are bleeding, injured, deeplyhooked, foul-hooked, or severely exhausted, but local fisheries' regulations must be obeyed. Fish that are released after being caught may be subjected to additional factors that influence their welfare, such as elevated stress, barotrauma, suppressed feeding and growth, impaired reproductive function, increased potential for disease, infection, and delayed mortality.
A Monetary Reward Alters Pacing but Not Performance in Competitive Cyclists

Money has frequently been used as an extrinsic motivator since it is assumed that humans are willing to invest more effort for financial reward. However, the influence of a monetary reward on pacing and performance in trained athletes is not well-understood. Therefore, the aim of this study was to analyse the influence of a monetary reward in well-trained cyclists on their pacing and performance during short and long cycling time trials (TT). Twentythree cyclists (6 ♀, 17 ♂) completed 4 self-paced time trials (TTs, 2 short: 4 km and 6 min; 2 long: 20 km and 30 min); in a randomized order. Participants were separated into parallel, non-randomized “rewarded” and “non-rewarded” groups. Cyclists in the rewarded group received a monetary reward based on highest mean power output across all TTs. Cyclists in the non-rewarded group did not receive a monetary reward. Overall performance was not significantly different between groups in short or long TTs (p > 0.48). Power output showed moderatly lower effect sizes at comencement of the short TTs (Pmeandiff = 36.6 W; d > 0.44) and the 20 km TT (Pmeandiff = 22.6 W; d = 0.44) in the rewarded group. No difference was observed in pacing during the 30 min TT (p = 0.95). An external reward seems to have influenced pacing at the commencement of time trials. Participants in the non-rewarded group adopted a typical parabolic shaped pattern, whereas participants in the rewarded group started trials more conservatively. Results raise the possibility that using money as an extrinsic reward may interfere with regulatory processes required for effective pacing.
Licensing of gametogenesis, dependent on RNA binding protein DAZL, as a gateway to sexual differentiation of fetal germ cells

Mammalian oocytes and spermatozoa derive from fetal cells shared by the sexes. These primordial germ cells (PGCs) migrate to the developing somatic gonad, giving rise to oocytes or spermatozoa. These opposing sexual fates are determined not by the PGCs’ own sex chromosome constitution (XX or XY), but by the sexual identity of the fetal gonad that they enter. We asked whether PGCs undergo a developmental transition that enables them to respond to feminizing or masculinizing cues from fetal ovary or testis. We conducted in vivo genetic studies of DAZL, an RNA-binding protein expressed in both ovarian and testicular germ cells. We found that germ cells in C57BL/6 Dazl-deficient fetuses—whether XX or XY—migrate to the gonad but do not develop either male or female features. Instead, they remain in a sexually undifferentiated state similar to that of migrating PGCs. Thus, germ cells in C57BL/6 Dazl-deficient fetuses do not respond to sexual cues from ovary or testis, whereas the earlier processes of germ cell specification and migration are unaffected. We propose that PGCs of both XX and XY fetuses undergo licensing, an active developmental transition that enables the resultant gametogenesis-competent cells to respond to feminizing or masculinizing cues produced by the fetal ovary or testis and hence to embark on oogenesis or spermatogenesis. In C57BL/6 mice, Dazl is required for licensing. Licensing serves as a gateway from the embryonic processes shared between the sexes—germ cell specification and migration—to the sex-specific pathways of oogenesis and spermatogenesis.
Theta Coordinated Error-Driven Learning in the Hippocampus

The learning mechanism in the hippocampus has almost universally been assumed to be Hebbian in nature, where individual neurons in an engram join together with synaptic weight increases to support facilitated recall of memories later. However, it is also widely known that Hebbian learning mechanisms impose significant capacity constraints, and are generally less computationally powerful than learning mechanisms that take advantage of error signals. We show that the differential phase relationships of hippocampal subfields within the overall theta rhythm enable a powerful form of error-driven learning, which results in significantly greater capacity, as shown in computer simulations. In one phase of the theta cycle, the bidirectional connectivity between CA1 and entorhinal cortex can be trained in an error-driven fashion to learn to effectively encode the cortical inputs in a compact and sparse form over CA1. In a subsequent portion of the theta cycle, the system attempts to recall an existing memory, via the pathway from entorhinal cortex to CA3 and CA1. Finally the full theta cycle completes when a strong target encoding representation of the current input is imposed onto the CA1 via direct projections from entorhinal cortex. The difference between this target encoding and the attempted recall of the same representation on CA1 constitutes an error signal that can drive the learning of CA3 to CA1 synapses. This CA3 to CA1 pathway is critical for enabling full reinstatement of recalled hippocampal memories out in cortex. Taken together, these new learning dynamics enable a much more robust, high-capacity model of hippocampal learning than was available previously under the classical Hebbian model.
Reuse-driven interprocedural slicing in the presence of pointers and recursion

Program slicing, a technique to compute the subset of program statements that can affect the value of a program variable at a specific program point, is widely used in tools to support maintenance activities. To be useful for supporting these activities, a slicing technique must be sufficiently precise and efficient. Harrold and Ci (1998) proposed a method for improving the efficiency of slicing by reusing slicing information for subsequent slicing. This paper presents an interprocedural slicing algorithm that improves the efficiency and precision of Harrold and Ci's algorithm for programs with pointer variables and recursion. Our empirical results show that our improvements can effectively achieve more reuse in slice computation, for programs with pointers, and can significantly reduce the sizes of slices, for programs with recursion.
Application and Modifications of Minimal Disease Activity Measures for Patients with Psoriatic Arthritis Treated with Adalimumab: Subanalyses of ADEPT

Objective. This posthoc analysis evaluated the percentage of patients with psoriatic arthritis (PsA) who achieved minimal disease activity (MDA) and compared the results with a modified MDA substituting the physician global assessment (PGA) for the Psoriasis Activity and Severity Index (PASI) using data from the ADalimumab Effectiveness in Psoriatic Arthritis Trial (ADEPT; NCT00646386). Methods. Patients with active PsA were randomized to receive adalimumab 40 mg or placebo every other week for 24 weeks. MDA was defined as achieving ≥ 5 of the following criteria: tender joint count ≤ 1; swollen joint count ≤ 1; PASI ≤ 1 or body surface area ≤ 3%; patient pain score ≤ 15 [1–100 mm visual analog scale (VAS)]; patient global assessment (PGA) of disease activity ≤ 20 (1–100 mm VAS); Health Assessment Questionnaire ≤ 0.5; and tender entheseal points ≤ 1 (only heels assessed). For modification of the MDA, PASI ≤ 1 was substituted with PGA “Clear” as MDAPGA1 and PGA “Clear” or “Almost clear” as MDAPGA2. Results. Sixty-seven patients were treated with adalimumab and 69 with placebo. At Week 24, MDA, MDAPGA1, and MDAPGA2 were achieved by 39%, 37%, and 39%, respectively, of patients treated with adalimumab versus 7%, 5%, and 8% of patients on placebo (p < 0.001). Kappa coefficients indicated good agreement between PASI and PGA at Week 24. Conclusion. ADEPT results indicated that significantly more patients treated with adalimumab achieved MDA by Week 24 compared with placebo. Modification of the MDA by replacing PASI ≤ 1 with PGA assessments did not alter the results, which may improve feasibility of practical use of the index.
Choline phospholipid metabolism: A target in cancer cells?

The experience of treating cancer over the past several decades overwhelmingly demonstrates that the disease continues to evade the vast array of drugs and treatment modalities available in the twenty‐first century. This is not surprising in view of the complexity of this disease, and the multiplicities of pathways available to the cancer cell to enable its survival. Although the progression of cancer arrives at a common end point of cachexia, organ failure, and death, common pathways are rare in cancer. Identifying and targeting common pathways that would act across these levels of multiplicity is essential for the successful treatment of this disease. Over the past decade, one common characteristic consistently revealed by magnetic resonance spectroscopic studies is the elevation of phosphocholine and total choline‐containing compounds in cancer cells and solid tumors. This elevation has been observed in almost every single cancer type studied with NMR spectroscopy and can be used as an endogenous biomarker of cancer. In this article, we have summarized some of the observations on the choline phospholipid metabolism of cancer cells and tumors, and make a case for targeting the aberrant choline phospholipid metabolism of cancer cells. © 2003 Wiley‐Liss, Inc.
Opportunistic and cooperative forwarding in mobile Ad-hoc networks with light-weight proactive source routing

The multi-hop wireless network has drawn a great deal of attention in the research community. Within the long period after it was proposed, the routing and forwarding operations in the multi-hop wireless network remain to be quite similar to those in the multi-hop wired network or the Internet. However, all the data transmission over the wireless medium in the wireless networks is by broadcasting in nature, which is different from the Internet. Because of the broadcast nature, many opportunities based on overhearing can be used to enhance the data transmission ability in wireless network. ExOR is the first practical data forwarding scheme which tries to promote the data transmission ability by utilizing the broadcast nature in wireless mesh networks, and the opportunistic data forwarding becomes a well-known term given by ExOR to name this kind of new data forwarding scheme. The basic idea in ExOR has triggered a great deal of derivations. However, almost all these derivations are proposed for wireless mesh networks or require the positioning service to support opportunistic data forwarding in the Mobile Ad-hoc Networks (MANETs). In this thesis, we propose a series of solutions to implement opportunistic data forwarding in more general MANETs, which is called Cooperative Opportunistic Routing in Mobile Ad-hoc Networks (CORMAN). CORMAN includes three following important components. First, a new light-weight proactive source routing scheme PSR is proposed to provide source routing information in MANETs for both opportunistic data forwarding and traditional IP forwarding. Second, we analyze and evaluate the topology change with mathematical model, and propose large-scale live update to update routing information more quickly with no extra communication overhead. Third, we propose the small-scale retransmission to utilize the broadcast nature one step further than ExOR, and furthermore it helps us to enhance the efficiency and robustness of the opportunistic date forwarding in MANETs. We run computer simulations in Network Simulator 2 (ns-2), and the simulation results indicate that the proposed solutions work well to support opportunistic data forwarding in MANETs. In particular, the routing overhead in PSR is only a small fraction of that in OLSR (Optimized Link State Routing), DSDV (Destination-Sequenced Distance Vector), and DSR (Dynamic Source Routing). Meanwhile, PSR has higher TCP (Transmission Control Protocol) throughput, much shorter packet end-to-end delay and delay variance than that in the three baseline protocols. Furthermore, a particular evaluation for the small-scale retransmission indicates us such a retransmission scheme can provide us up to 15% gains on the Packet Delivery Ratio (PDR) with UDP (User Datagram Protocol) data flows. At last, when we compare CORMAN as a system to AODV, we find the PDR in CORMAN is up to 4 times of the PDR in AODV.
Shard ranking and cutoff estimation for topically partitioned collections

Large document collections can be partitioned into 'topical shards' to facilitate distributed search. In a low-resource search environment only a few of the shards can be searched in parallel. Such a search environment faces two intertwined challenges. First, determining which shards to consult for a given query: shard ranking. Second, how many shards to consult from the ranking: cutoff estimation. In this paper we present a family of three algorithms that address both of these problems. As a basis we employ a commonly used data structure, the central sample index (CSI), to represent the shard contents. Running a query against the CSI yields a flat document ranking that each of our algorithms transforms into a tree structure. A bottom up traversal of the tree is used to infer a ranking of shards and also to estimate a stopping point in this ranking that yields cost-effective selective distributed search. As compared to a state-of-the-art shard ranking approach the proposed algorithms provide substantially higher search efficiency while providing comparable search effectiveness.
Cerebral control of face, jaw, and tongue movements in awake cats: Changes in regional cerebral blood flow during lateral feeding

Mastication is achieved by cooperation among facial, masticatory, and lingual muscles. However, cortical control in cats for the masticatory performance is processed by two systems: facial movement processed by facial SI (the first somatosensory cortex), area C, and area M (motor areas), and jaw and tongue movements performed by intraoral SI, masticatory area, and area P (motor area). In particular, outputs from area P organized in the corticobulbar tract are projected bilaterally in the brainstem. In this present study, the aim is to explore changes in the regional cerebral blood flow (rCBF) in the facial SI, area M, and area P during trained lateral feeding (licking or chewing from the right or left side) of milk, fish paste, and small dry fish. The rCBF in area M showed contralateral dominance, and rCBF in area P during chewing or licking from the right or left side was almost the same value. Furthermore, activities of genioglossus and masseter muscles in the left side showed almost the same values during licking of milk and of fish paste, and chewing of small dry fish during lateral feeding. These findings suggest that the cortical process for facial, jaw, and tongue movements may be regulated by the contralateral dominance of area M and the bilateral one of area P.
Role of Inducible Nitric Oxide Synthase in the Pulmonary Vascular Response to Birth-Related Stimuli in the Ovine Fetus

To determine whether type II nitric oxide synthase (NOS II) contributes to the NO-mediated fall in pulmonary vascular resistance (PVR) at birth, we studied the effects of selective NOS II antagonists N-(3-aminomethyl) benzylacetamidine dihydrochloride (1400W) and aminoguanidine (AG) and a nonselective NOS antagonist, nitro-l-arginine (L-NA), during mechanical ventilation with low Fio2 (<10%), high Fio2 (100%), and inhaled NO (20 ppm) in 23 near-term fetal lambs. Intrapulmonary infusions of AG, 1400W, and L-NA increased basal PVR before delivery (P <0.05). In control animals, ventilation with low and high Fio2 decreased PVR by 62% and 85%, respectively. Treatment with AG and 1400W attenuated the fall in PVR by 50% during ventilation with low and high Fio2 (control versus treatment, P <0.05 for each intervention). L-NA treatment attenuated the fall in PVR during ventilation with low and high Fio2 to a similar degree as the NOS II antagonists. To test the selectivity of the NOS II antagonists, we studied the effects of acetylcholine and inhaled NO in each study group. Acetylcholine-induced pulmonary vasodilation remained intact after treatment with selective NOS II antagonists but not after treatment with nonselective NOS blockade with L-NA. In contrast, the response to inhaled NO was similar between treatment groups. We conclude that selective NOS II inhibition is as effective as nonselective NOS blockade in attenuating pulmonary vasodilation at birth and speculate that NOS II activity contributes to NO-mediated pulmonary vasodilation at birth. We additionally speculate that stimulation of the airway epithelium by rhythmic distension and increased Fio2 may activate NOS II release at birth.